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11 - Molecular genetics of acute myeloid leukemia

from Part II - Cell biology and pathobiology

Published online by Cambridge University Press:  01 July 2010

By
Robert B. Lorsbach  and
James R. Downing
Edited by
Ching-Hon Pui
Robert B. Lorsbach
Affiliation:
Assistant Member, Department of Pathology St. Jude Children's Research Hospital, St. Jude Children's Research Hospital, Memphis, TN, USA
James R. Downing
Affiliation:
Member and Chair, Department of Pathology, Scientific Director, St. Jude Children's Research Hospital, Memphis, TN, USA
Ching-Hon Pui
Affiliation:
St. Jude Children's Research Hospital, Memphis
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Summary

Introduction

One of the goals of modern leukemia research has been to gain a clearer understanding of the nature of the underlying molecular genetic lesions responsible for the establishment of the leukemic clone. This pursuit is fueled by the hope that the information obtained will not only help us understand the variability in clinical response that is observed among leukemia patients, but will also lead to the identification of rational molecular targets for novel chemotherapeutic agents. This goal is starting to be realized through recent advances in our understanding of the pathogenesis of acute myeloid leukemia (AML). Specifically, molecular genetic and genomic data are beginning to provide the initial framework for the subclassification of AML into clinically meaningful subgroups, and rationally designed compounds that inhibit novel molecular targets in leukemic cells are beginning to be assessed clinically for their utility as antileukemic therapeutics.

In this chapter, we provide a summary of the recent advances that have been made in elucidating the molecular genetic lesions involved in the pathogenesis of de novo AML. Our approach is to describe the structure of identified genetic lesions and explain at a molecular level how these alterations lead to cellular transformation. Because of the distinct clinical and biologic differences that exist between de novo AML and myelodysplasia-related AML, we largely restrict our discussion to de novo AML, which lacks any evidence of a prior or concurrent myelodysplastic phase.

Type
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Information
Childhood Leukemias , pp. 298 - 338
Publisher: Cambridge University Press
Print publication year: 2006

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References

Karp, J. E. & Smith, M. A.The molecular pathogenesis of treatment-induced (secondary) leukemias: foundations for treatment and prevention. Semin Oncol, 1997; 24: 103–13.Google ScholarPubMed
Creutzig, U., Ritter, J., Vormoor, J., et al.Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM study group. Leukemia, 1996; 10: 1677–86.Google ScholarPubMed
Jaffe, E. S., Harris, N. L., Stein, H., & Vardiman, J. W., eds. Pathology and genetics of tumours of haematopoietic and lymphoid tissues (Lyon, France: IARC Press, 2001).Google Scholar
Bonnet, D. & Dick, J. E.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997; 3: 730–7.CrossRefGoogle ScholarPubMed
Look, A. T.Oncogenic transcription factors in the human acute leukemias. Science, 1997; 278: 1059–64.CrossRefGoogle ScholarPubMed
de The, H., Chomienne, C., Lanotte, M., Degos, L., & Dejean, A.The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature, 1990; 347: 558–61.CrossRefGoogle Scholar
Borrow, J., Goddard, A. D., Sheer, D., & Solomon, E.Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science, 1990; 249: 1577–80.CrossRefGoogle ScholarPubMed
Alcalay, M., Zangrilli, D., Pandolfi, P. P., et al.Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus. Proc Natl Acad Sci U S A, 1991; 88: 1977–81.CrossRefGoogle ScholarPubMed
de The, H., Lavau, C., Marchio, A., et al.The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell, 1991; 66: 675–84.CrossRefGoogle Scholar
Kakizuka, A., Miller, W. H. J., Umesono, K., et al.Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell, 1991; 66: 663–74.CrossRefGoogle Scholar
Grimwade, D. & Solomon, E.Characterisation of the PML/RAR alpha rearrangement associated with t(15;17) acute promyelocytic leukaemia. Curr Top Microbiol Immunol, 1997; 220: 81–112.Google Scholar
Biondi, A., Rambaldi, A., Pandolfi, P. P., et al.Molecular monitoring of the myl/retinoic acid receptor-α fusion gene in acute promyelocytic leukemia by polymerase chain reaction. Blood, 1992; 80: 492–7.Google ScholarPubMed
Pollock, J. L., Westervelt, P., Kurichety, A. K., et al.A bcr-3 isoform of RARalpha-PML potentiates the development of PML-RARalpha-driven acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 1999; 96: 15103–8.CrossRefGoogle ScholarPubMed
He, L. Z., Bhaumik, M., Tribioli, C., et al.Two critical hits for promyelocytic leukemia. Mol Cell, 2000; 6: 1131–41.CrossRefGoogle ScholarPubMed
Chambon, P.A decade of molecular biology of retinoic acid receptors. FASEB J, 1996; 10: 940–54.CrossRefGoogle ScholarPubMed
Borden, K. L., Boddy, M. N., Lally, J., et al.The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J, 1995; 14: 1532–41.Google ScholarPubMed
Joazeiro, C. A. & Weissman, A. M.RING finger proteins: mediators of ubiquitin ligase activity. Cell, 2000; 102: 549–52.CrossRefGoogle ScholarPubMed
Saurin, A. J., Borden, K. L., Boddy, M. N., & Freemont, P. S.Does this have a familiar RING ?Trends Biochem Sci, 1996; 21: 208–14.CrossRefGoogle ScholarPubMed
Jensen, K., Shiels, C., & Freemont, P. S.PML protein isoforms and the RBCC/TRIM motif. Oncogene, 2001; 20: 7223–33.CrossRefGoogle ScholarPubMed
Fagioli, M., Alcalay, M., Pandolfi, P. P., et al.Alternative splicing of PML transcripts predicts coexpression of several carboxy-terminally different protein isoforms. Oncogene, 1992; 7: 1083–91.Google ScholarPubMed
Tashiro, S., Kotomura, N., Tanaka, K., et al.Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15:17 chromosomal translocation of acute promyelocytic leukemia. Oncogene, 1994; 9: 1939–45.Google ScholarPubMed
Pandolfi, P. P., Alcalay, M., Fagioli, M., et al.Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia. EMBO J, 1992; 11: 1397–1407.Google ScholarPubMed
Gallagher, R. E., Li, Y. P., Rao, S., et al.Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid. Blood, 1995; 86: 1540–7.Google ScholarPubMed
Fukutani, H., Naoe, T., Ohno, R., et al.Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. The Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia, 1995; 9: 1478–82.Google Scholar
Gu, B. W., Xiong, H., Zhou, Y., et al.Variant-type PML-RAR(alpha) fusion transcript in acute promyelocytic leukemia: use of a cryptic coding sequence from intron 2 of the RAR(alpha) gene and identification of a new clinical subtype resistant to retinoic acid therapy. Proc Natl Acad Sci U S A, 2002; 99: 7640–5.CrossRefGoogle ScholarPubMed
Pandolfi, P. P.PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia. Haematologica, 1996; 81: 472–82.Google ScholarPubMed
Leid, M., Kastner, P., Lyons, R., et al.Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell, 1992; 68: 377–95.CrossRefGoogle ScholarPubMed
Horlein, A. J., Naar, A. M., Heinzel, T., et al.Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature, 1995; 377: 397–404.CrossRefGoogle ScholarPubMed
Kurokawa, R., Soderstrom, M., Horlein, A., et al.Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature, 1995; 377: 451–4.CrossRefGoogle ScholarPubMed
Nagy, L., Kao, H. Y., Chakravarti, D., et al.Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell, 1997; 89: 373–80.CrossRefGoogle ScholarPubMed
Grunstein, M.Histone acetylation in chromatin structure and transcription. Nature, 1997; 389: 349–52.CrossRefGoogle ScholarPubMed
Kamei, Y., Xu, L., Heinzel, T., et al.A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell, 1996; 85: 403–14.CrossRefGoogle ScholarPubMed
Shikama, N., Lyon, J., & La Thangue, N.The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol, 1997; 7: 230–6.CrossRefGoogle Scholar
Kawasaki, H., Eckner, R., Yao, T. P., et al.Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation. Nature, 1998; 393: 284–9.CrossRefGoogle ScholarPubMed
Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., & Nakatani, Y.The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell, 1996; 87: 953–9.CrossRefGoogle ScholarPubMed
Chen, H., Lin, R. J., Schiltz, R. L., et al.Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 1997; 90: 569–80.CrossRefGoogle Scholar
Pazin, M. J. & Kadonaga, J. T.What's up and down with histone deacetylation and transcription ?Cell, 1997; 89: 325–8.CrossRefGoogle Scholar
Rhodes, D.Chromatin structure. The nucleosome core all wrapped up [news]. Nature, 1997; 389: 231–3.CrossRefGoogle Scholar
Gu, W. & Roeder, R. G.Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell, 1997; 90: 595–606.CrossRefGoogle ScholarPubMed
Weis, K., Rambaud, S., Lavau, C., et al.Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell, 1994; 76: 345–56.CrossRefGoogle ScholarPubMed
Dyck, J. A., Maul, G. G., Miller, W. H., et al.A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell, 1994; 76: 333–43.CrossRefGoogle ScholarPubMed
Lamond, A. I. & Earnshaw, W. C.Structure and function in the nucleus. Science, 1998; 280: 547–53.CrossRefGoogle ScholarPubMed
Grotzinger, T., Sternsdorf, T., Jensen, K., & Will, H.Interferon-modulated expression of genes encoding the nuclear-dot-associated proteins Sp100 and promyelocytic leukemia protein (PML). Eur J Biochem, 1996; 238: 554–60.CrossRefGoogle Scholar
Chen, Z., Brand, N. J., Chen, A., et al.Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J, 1993; 12: 1161–7.Google Scholar
Koken, M. H., Reid, A., Quignon, F., et al.Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. Proc Natl Acad Sci U S A, 1997; 94: 10 255–60.CrossRefGoogle ScholarPubMed
Ruthardt, M., Orleth, A., Tomassoni, L., et al.The acute promyelocytic leukaemia specific PML and PLZF proteins localize to adjacent and functionally distinct nuclear bodies. Oncogene, 1998; 16: 1945–53.CrossRefGoogle ScholarPubMed
Everett, R. D., Meredith, M., Orr, A., et al.A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J, 1997; 16: 1519–30.CrossRefGoogle ScholarPubMed
Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., & Freemont, P. S.PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia. Oncogene, 1996; 13: 971–82.Google Scholar
Doucas, V., Tini, M., Egan, D. A., & Evans, R. M.Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling. Proc Natl Acad Sci U S A, 1999; 96: 2627–32.CrossRefGoogle ScholarPubMed
Zhong, S., Muller, S., Ronchetti, S., et al.Role of SUMO-1-modified PML in nuclear body formation. Blood, 2000; 95: 2748–52.Google ScholarPubMed
Zhong, S., Salomoni, P., & Pandolfi, P. P.The transcriptional role of PML and the nuclear body. Nat Cell Biol, 2000; 2: E85–90.CrossRefGoogle ScholarPubMed
Best, J. L., Ganiatsas, S., Agarwal, S., et al.SUMO-1 protease-1 regulates gene transcription through PML. Mol Cell, 2002; 10: 843–55.CrossRefGoogle ScholarPubMed
Borden, K. L., Lally, J. M., Martin, S. R., et al.In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. Proc Natl Acad Sci U S A, 1996; 93: 1601–6.CrossRefGoogle ScholarPubMed
Borden, K. L., Campbell-Dwyer, E. J., & Salvato, M. S.The promyelocytic leukemia protein PML has a pro-apoptotic activity mediated through its RING domain. FEBS Lett, 1997; 418: 30–4.CrossRefGoogle Scholar
Le, X. F., Yang, P., & Chang, K. S.Analysis of the growth and transformation suppressor domains of promyelocytic leukemia gene, PML. J Biol Chem, 1996; 271: 130–5.CrossRefGoogle ScholarPubMed
Mu, Z. M., Chin, K. V., Liu, J. H., Lozano, G., & Chang, K. S.PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol, 1994; 14: 6858–67.CrossRefGoogle ScholarPubMed
Liu, J. H., Mu, Z. M., & Chang, K. S.PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu. J Exp Med, 1995; 181: 1965–73.CrossRefGoogle ScholarPubMed
Wang, Z. G., Delva, L., Gaboli, M., et al.Role of PML in cell growth and the retinoic acid pathway. Science, 1998; 279: 1547–51.CrossRefGoogle ScholarPubMed
Ferbeyre, G., de Stanchina, E., Querido, E., et al.PML is induced by oncogenic ras and promotes premature senescence. Genes Dev, 2000; 14: 2015–27.Google ScholarPubMed
Pearson, M., Carbone, R., Sebastiani, C., et al.PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature, 2000; 406: 207–10.CrossRefGoogle ScholarPubMed
Fang, W., Mori, T., & Cobrinik, D.Regulation of PML-dependent transcriptional repression by pRB and low penetrance pRB mutants. Oncogene, 2002; 21: 5557–65.CrossRefGoogle ScholarPubMed
Alcalay, M., Tomassoni, L., Colombo, E., et al.The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein. Mol Cell Biol, 1998; 18: 1084–93.CrossRefGoogle ScholarPubMed
Wang, Z. G., Ruggero, D., Ronchetti, S., et al.PML is essential for multiple apoptotic pathways. Nat Genet, 1998; 20: 266–72.CrossRefGoogle ScholarPubMed
Guo, A., Salomoni, P., Luo, J., et al.The function of PML in p53-dependent apoptosis. Nat Cell Biol, 2000; 2: 730–6.CrossRefGoogle ScholarPubMed
Yang, S., Kuo, C., Bisi, J. E., & Kim, M. K.PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat Cell Biol, 2002; 4: 865–70.CrossRefGoogle ScholarPubMed
Guiochon-Mantel, A., Savouret, J. F., Quignon, F., et al.Effect of PML and PML-RAR on the transactivation properties and subcellular distribution of steroid hormone receptors. Mol Endocrinol, 1995; 9: 1791–1803.Google ScholarPubMed
Grignani, F., Ferrucci, P. F., Testa, U., et al.The acute promyelocytic leukemia-specific PML-RAR alpha fusion protein inhibits differentiation and promotes survival of myeloid precursor cells. Cell, 1993; 74: 423–31.CrossRefGoogle ScholarPubMed
Grignani, F., Testa, U., Fagioli, M., et al.Promyelocytic leukemia-specific PML-retinoic acid alpha receptor fusion protein interferes with erythroid differentiation of human erythroleukemia K562 cells. Cancer Res, 1995; 55: 440–3.Google ScholarPubMed
Grignani, F., Testa, U., Rogaia, D., et al.Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains. EMBO J, 1996; 15: 4949–58.Google ScholarPubMed
Lin, R. J. & Evans, R. M.Acquisition of oncogenic potential by RAR chimeras in acute promyelocytic leukemia through formation of homodimers. Mol Cell, 2000; 5: 821–30.CrossRefGoogle ScholarPubMed
Minucci, S., Maccarana, M., Cioce, M., et al.Oligomerization of RAR and AML1 transcription factors as a novel mechanism of oncogenic activation. Mol Cell, 2000; 5: 811–20.CrossRefGoogle ScholarPubMed
Koken, M. H. M., Puvion-Dutilleul, F., Guillemin, M. C., et al.The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J, 1994; 13: 1073–83.Google Scholar
Fu, S., Consoli, U., Hanania, E. G., et al.PML/RARalpha, a fusion protein in acute promyelocytic leukemia, prevents growth factor withdrawal-induced apoptosis in TF-1 cells. Clin Cancer Res, 1995; 1: 583–90.Google ScholarPubMed
Maeda, Y., Horiuchi, F., Miyatake, J., et al.Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RAR alpha fusion gene. Br J Haematol, 1996; 93: 973–6.CrossRefGoogle ScholarPubMed
Rogaia, D., Grignani, F., Nicoletti, I., & Pelicci, P. G.The acute promyelocytic leukemia-specific PML/RAR alpha fusion protein reduces the frequency of commitment to apoptosis upon growth factor deprivation of GM-CSF-dependent myeloid cells. Leukemia, 1995; 9: 1467–72.Google ScholarPubMed
Rousselot, P., Hardas, B., Patel, A., et al.The PML-RAR alpha gene product of the t(15;17) translocation inhibits retinoic acid-induced granulocytic differentiation and mediated transactivation in human myeloid cells. Oncogene, 1994; 9: 545–51.Google Scholar
Rego, E. M., Wang, Z. G., Peruzzi, D., et al.Role of promyelocytic leukemia (PML) protein in tumor suppression. J Exp Med, 2001; 193: 521–9.CrossRefGoogle ScholarPubMed
Kogan, S. C., Brown, D. E., Shultz, D. B., et al.BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor alpha chimeric protein (PMLRARalpha) to block neutrophil differentiation and initiate acute leukemia. J Exp Med, 2001; 193: 531–43.CrossRefGoogle ScholarPubMed
Di Croce, L., Raker, V. A., Corsaro, M., et al.Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science, 2002; 295: 1079–82.CrossRefGoogle ScholarPubMed
Lane, A. A. & Ley, T. J.Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice. Cell, 2003; 115: 305–18.CrossRefGoogle ScholarPubMed
Grignani, F., De Matteis, S., Nervi, C., et al.Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature, 1998; 391: 815–18.CrossRefGoogle ScholarPubMed
Lin, R. J., Nagy, L., Inoue, S., et al.Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature, 1998; 391: 811–14.CrossRefGoogle ScholarPubMed
He, L. Z., Guidez, F., Tribioli, C., et al.Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat Genet, 1998; 18: 126–35.CrossRefGoogle ScholarPubMed
Raelson, J. V., Nervi, C., Rosenauer, A., et al.The PML/RAR alpha oncoprotein is a direct molecular target of retinoic acid in acute promyelocytic leukemia cells. Blood, 1996; 88: 2826–32.Google ScholarPubMed
Hong, S. H., David, G., Wong, C. W., Dejean, A., & Privalsky, M. L.SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 1997; 94: 9028–33.CrossRefGoogle ScholarPubMed
Collins, S. J.Acute promyelocytic leukemia: relieving repression induces remission. Blood, 1998; 91: 2631–3.Google ScholarPubMed
Tobal, K., Saunders, M. J., Grey, M. R., & Yin, J. A.Persistence of RAR alpha-PML fusion mRNA detected by reverse transcriptase polymerase chain reaction in patients in long-term remission of acute promyelocytic leukaemia. Br J Haematol, 1995; 90: 615–18.CrossRefGoogle ScholarPubMed
Nervi, C., Ferrara, F. F., Fanelli, M., et al.Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood, 1998; 92: 2244–51.Google ScholarPubMed
Zhu, J., Gianni, M., Kopf, E., et al.Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci U S A, 1999; 96: 14 807–12.CrossRefGoogle ScholarPubMed
Jing, Y., Xia, L., Lu, M., & Waxman, S.The cleavage product deltaPML-RARalpha contributes to all-trans retinoic acid-mediated differentiation in acute promyelocytic leukemia cells. Oncogene, 2003; 22: 4083–91.CrossRefGoogle ScholarPubMed
Yuan, W. & Krug, R. M.Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J, 2001; 20: 362–71.CrossRefGoogle ScholarPubMed
Kitareewan, S., Pitha-Rowe, I., Sekula, D., et al.UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 2002; 99: 3806–11.CrossRefGoogle ScholarPubMed
Malakhova, O. A., Yan, M., Malakhov, M. P., et al.Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev, 2003; 17: 455–60.CrossRefGoogle ScholarPubMed
Dermime, S., Grignani, F., Clerici, M., et al.Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RAR alpha protein. Blood, 1993; 82: 1573–7.Google ScholarPubMed
Shao, W., Benedetti, L., Lamph, W. W., Nervi, C., & Miller, W. H. J.A retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant negative PML-RAR alpha mutation. Blood, 1997; 89: 4282–9.Google ScholarPubMed
Zhou, D. C., Kim, S. H., Ding, W., et al.Frequent mutations in the ligand-binding domain of PML-RARalpha after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo. Blood, 2002; 99: 1356–63.CrossRefGoogle ScholarPubMed
Tallman, M. S., Nabhan, C., Feusner, J. H., & Rowe, J. M.Acute promyelocytic leukemia: evolving therapeutic strategies. Blood, 2002; 99: 759–67.CrossRefGoogle ScholarPubMed
Shao, W., Fanelli, M., Ferrara, F. F., et al.Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells. J Natl Cancer Inst, 1998; 90: 124–33.CrossRefGoogle ScholarPubMed
Zhu, J., Koken, M. H., Quignon, F., et al.Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc Natl Acad Sci U S A, 1997; 94: 3978–83.CrossRefGoogle ScholarPubMed
Look, A. T.Arsenic and apoptosis in the treatment of acute promyelocytic leukemia [editorial]. J Natl Cancer Inst, 1998; 90: 86–8.CrossRefGoogle Scholar
Early, E., Moore, M. A., Kakizuka, A., et al.Transgenic expression of PML/RARalpha impairs myelopoiesis. Proc Natl Acad Sci U S A, 1996; 93: 7900–4.CrossRefGoogle ScholarPubMed
Altabef, M., Garcia, M., Lavau, C., et al.A retrovirus carrying the promyelocyte-retinoic acid receptor PML- RARalpha fusion gene transforms haematopoietic progenitors in vitro and induces acute leukaemias. EMBO J, 1996; 15: 2707–16.Google ScholarPubMed
Grisolano, J. L., Wesselschmidt, R. L., Pelicci, P. G., & Ley, T. J.Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR alpha under control of cathepsin G regulatory sequences. Blood, 1997; 89: 376–87.Google ScholarPubMed
He, L. Z., Tribioli, C., Rivi, R., et al.Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice. Proc Natl Acad Sci U S A, 1997; 94: 5302–7.CrossRefGoogle ScholarPubMed
Le Beau, M. M., Davis, E. M., Patel, B., et al.Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice identify cooperating events and genetic pathways to acute promyelocytic leukemia. Blood, 2003; 102: 1072–4.CrossRefGoogle ScholarPubMed
Zimonjic, D. B., Pollock, J. L., Westervelt, P., Popescu, N. C., & Ley, T. J.Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice. Proc Natl Acad Sci U S A, 2000; 97: 13 306–11.CrossRefGoogle ScholarPubMed
Redner, R. L., Rush, E. A., Faas, S., Rudert, W. A., & Corey, S. J.The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood, 1996; 87: 882–6.Google Scholar
Wells, R. A., Catzavelos, C., & Kamel-Reid, S.Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet, 1997; 17: 109–13.CrossRefGoogle ScholarPubMed
Arnould, C., Philippe, C., Bourdon, V., et al.The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Hum Mol Genet, 1999; 8: 1741–9.CrossRefGoogle ScholarPubMed
Redner, R. L.Variations on a theme: the alternate translocations in APL. Leukemia, 2002; 16: 1927–32.CrossRefGoogle ScholarPubMed
Avantaggiato, V., Pandolfi, P. P., Ruthardt, M., et al.Developmental analysis of murine Promyelocytic Leukemia Zinc Finger (PLZF) gene expression: implications for the neuromeric model of the forebrain organization. J Neurosci, 1995; 15: 4927–42.CrossRefGoogle ScholarPubMed
Cook, M., Gould, A., Brand, N., et al.Expression of the zinc-finger gene PLZF at rhombomere boundaries in the vertebrate hindbrain. Proc Natl Acad Sci U S A, 1995; 92: 2249–53.CrossRefGoogle ScholarPubMed
Ruthardt, M., Testa, U., Nervi, C., et al.Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling. Mol Cell Biol, 1997; 17: 4859–69.CrossRefGoogle ScholarPubMed
Dong, S., Zhu, J., Reid, A., et al.Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger- retinoic acid receptor-alpha fusion protein. Proc Natl Acad Sci U S A, 1996; 93: 3624–9.CrossRefGoogle ScholarPubMed
Melnick, A., Carlile, G., Ahmad, K. F., et al.Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors. Mol Cell Biol, 2002; 22: 1804–18.CrossRefGoogle ScholarPubMed
Chen, Z., Guidez, F., Rousselot, P., et al.PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Proc Natl Acad Sci U S A, 1994; 91: 1178–82.CrossRefGoogle Scholar
Lo, C. F., Pisegna, S., & Diverio, D.The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias. Haematologica, 1997; 82: 364–70.Google Scholar
Miyoshi, H., Shimizu, K., Kozu, T., et al.t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A, 1991; 88: 10431–4.CrossRefGoogle Scholar
Erickson, P., Gao, J., Chang, K. S., et al.Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood, 1992; 80: 1825–31.Google Scholar
Nisson, P. E., Watkins, P. C., & Sacchi, N.Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells [published erratum appears in Cancer Genet Cytogenet, 1993; 66: 81]. Cancer Genet Cytogenet, 1992; 63: 81–8.CrossRefGoogle Scholar
Miyoshi, H., Kozu, T., Shimizu, K., et al.The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J, 1993; 12: 2715–21.Google Scholar
Liu, P., Tarle, S. A., Hajra, A., et al.Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science, 1993; 261: 1041–4.CrossRefGoogle Scholar
Berger, R., Bernheim, A., Ochoa-Noguera, M. E., et al.Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients. Cancer Genet Cytogenet, 1987; 28: 293–9.CrossRefGoogle ScholarPubMed
Samuels, B. L., Larson, R. A., LeBeau, M. M., et al.Specific chromosomal abnormalities in acute nonlymphocytic leukemia correlate with drug susceptibility in vivo. Leukemia, 1988; 2: 79–83.Google ScholarPubMed
Keating, M. J., Smith, T. L., Kantarjian, H., et al.Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. Leukemia, 1988; 2: 403–12.Google Scholar
Fenaux, P., Preudhomme, C., Lai, J. L., et al.Cytogenetics and their prognostic value in de novo acute myeloid leukemia: a report on 283 cases. Br J Haematol, 1989; 73: 61–7.CrossRefGoogle ScholarPubMed
Dastugue, N., Payen, C., Lafage-Pochitaloff, M., et al.Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group. Leukemia, 1995; 9: 1491–8.Google ScholarPubMed
Nucifora, G., Birn, D. J., Espinosa, R., et al.Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood, 1993; 81: 2728–34.Google Scholar
Golub, T. R., Barker, G. F., Bohlander, S. K., et al.Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A, 1995; 92: 4917–21.CrossRefGoogle ScholarPubMed
Romana, S. P., Mauchauffe, M., Le Coniat, M., et al.The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood, 1995; 85: 3662–70.Google Scholar
Wang, S., Wang, Q., Crute, B. E., et al.Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol Cell Biol, 1993; 13: 3324–39.CrossRefGoogle ScholarPubMed
Sun, W., O'Connell, M., & Speck, N. A.Characterization of a protein that binds multiple sequences in mammalian type C retrovirus enhancers. J Virol, 1993; 67: 1976–86.Google ScholarPubMed
Meyers, S., Downing, J. R., & Hiebert, S. W.Identification of AML-1 and the (8;21) translocation protein (AML- 1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein–protein interactions. Mol Cell Biol, 1993; 13: 6336–45.CrossRefGoogle ScholarPubMed
Daga, A., Tighe, J. E., & Calabi, F.Leukemia/Drosophila homology. Nature, 1992; 356: 484.CrossRefGoogle ScholarPubMed
Ogawa, E., Maruyama, M., Kagoshima, H., et al.PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc Natl Acad Sci U S A, 1993; 90: 6859–63.CrossRefGoogle ScholarPubMed
Levanon, D., Negreanu, V., Bernstein, Y., et al.AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics, 1994; 23: 425–32.CrossRefGoogle ScholarPubMed
Lorsbach, R. B., Moore, J., Ang, S. O., et al.Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression. Blood, 2004; 103: 2522–9.CrossRefGoogle ScholarPubMed
North, T. E., Stacy, T., Matheny, C. J., Speck, N. A., de Bruijn, M. F.Runx1 is expressed in adult mouse hematopoietic stem cells and differentiating myeloid and lymphoid cells, but not in maturing erythroid cells. Stem Cells, 2004; 22: 158–68.CrossRefGoogle ScholarPubMed
Corsetti, M. T. & Calabi, F.Lineage- and stage-specific expression of runt box polypeptides in primitive and definitive hematopoiesis. Blood, 1997; 89: 2359–68.Google ScholarPubMed
Levanon, D., Brenner, O., Negreanu, V., et al.Spatial and temporal expression pattern of Runx3 (Aml2) and Runx1 (Aml1) indicates non-redundant functions during mouse embryogen esis. Mech Dev, 2001; 109: 413–17.CrossRefGoogle Scholar
Theriault, F. M., Roy, P., & Stifani, S.AML1/Runx1 is important for the development of hindbrain cholinergic branchiovisceral motor neurons and selected cranial sensory neurons. Proc Natl Acad Sci U S A, 2004; 101: 10343–8.CrossRefGoogle ScholarPubMed
Ogawa, E., Inuzuka, M., Maruyama, M., et al.Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology, 1993; 194: 314–31.CrossRefGoogle ScholarPubMed
Huang, G., Shigesada, K., Ito, K., et al.Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin- proteasome-mediated degradation. EMBO J, 2001; 20: 723–33.CrossRefGoogle ScholarPubMed
Tanaka, Y., Watanabe, T., Chiba, N., et al.The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures. Oncogene, 1997; 15: 677–83.CrossRefGoogle ScholarPubMed
Lu, J., Maruyama, M., Satake, M., et al.Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF. Mol Cell Biol, 1995; 15: 1651–61.CrossRefGoogle ScholarPubMed
Chiba, N., Watanabe, T., Nomura, S., et al.Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2beta/CBFbeta, in muscle development. Oncogene, 1997; 14: 2543–52.CrossRefGoogle ScholarPubMed
Nuchprayoon, I., Meyers, S., Scott, L. M., et al.PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells. Mol Cell Biol, 1994; 14: 5558–68.CrossRefGoogle ScholarPubMed
Zhang, D. E., Fujioka, K., Hetherington, C. J., et al.Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). Mol Cell Biol, 1994; 14: 8085–95.CrossRefGoogle Scholar
Hsiang, Y. H., Spencer, D., Wang, S., Speck, N. A., & Raulet, D. H.The role of viral enhancer “core” motif-related sequences in regulating T cell receptor-γ and -δ gene expression. J Immunol, 1993; 150: 3905–16.Google ScholarPubMed
Shoemaker, S. G., Hromas, R., & Kaushansky, K.Transcriptional regulation of interleukin 3 gene expression in T lymphocytes [abstract]. Proc Natl Acad Sci U S A, 1990; 87: 9650–4.CrossRefGoogle Scholar
Takahashi, A., Satake, M., Yamaguchi-Iwai, Y., et al.Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2. Blood, 1995; 86: 607–16.Google ScholarPubMed
Wotton, D., Ghysdael, J., Wang, S., Speck, N. A., & Owen, M. J.Cooperative binding of Ets-1 and core binding factor to DNA. Mol Cell Biol, 1994; 14: 840–50.CrossRefGoogle Scholar
Hernandez-Munain, C. & Krangel, M. S.c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor delta enhancer [published erratum appears in Mol Cell Biol, 1995; 15: 4659]. Mol Cell Biol, 1995; 15: 3090–9.CrossRefGoogle Scholar
Britos-Bray, M. & Friedman, A. D.Core binding factor cannot synergistically activate the myeloperoxidase proximal enhancer in immature myeloid cells without c- Myb. Mol Cell Biol, 1997; 17: 5127–35.CrossRefGoogle ScholarPubMed
Erman, B., Cortes, M., Nikolajczyk, B. S., Speck, N. A., & Sen, R.ETS-core binding factor: a common composite motif in antigen receptor gene enhancers. Mol Cell Biol, 1998; 18: 1322–30.CrossRefGoogle ScholarPubMed
Carey, M.The enhanceosome and transcriptional synergy. Cell, 1998; 92: 5–8.CrossRefGoogle ScholarPubMed
Giese, K., Kingsley, C., Kirshner, J. R., & Grosschedl, R.Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. Genes Dev, 1995; 9: 995–1008.CrossRefGoogle ScholarPubMed
Bruhn, L., Munnerlyn, A., & Grosschedl, R.ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function. Genes Dev, 1997; 11: 640–53.CrossRefGoogle ScholarPubMed
Kurokawa, M., Tanaka, T., Tanaka, K., et al.Overexpression of the AML1 proto-oncoprotein in NIH3T3 cells leads to neoplastic transformation depending on the DNA-binding and transactivational potencies. Oncogene, 1996; 12: 883–92.Google ScholarPubMed
Aronson, B. D., Fisher, A. L., Blechman, K., Caudy, M., & Gergen, J. P.Groucho-dependent and -independent repression activities of Runt domain proteins. Mol Cell Biol, 1997; 17: 5581–7.CrossRefGoogle ScholarPubMed
Ahn, M. Y., Huang, G., Bae, S. C., et al.Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dcl3 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO. Proc Natl Acad Sci U S A, 1998; 95: 1812– 17.CrossRefGoogle Scholar
Kanno, T., Kanno, Y., Chen, L.-F., et al.Intrinsic transcriptional activation-inhibition domains of the polyomavirus enhancer binding protein 2/core binding factor α subunit revealed in the presence of the β subunit. Mol Cell Biol, 1998; 18: 2444–54.CrossRefGoogle ScholarPubMed
Nishimura, M., Fukushima-Nakase, Y., Fujita, Y., et al.VWRPY motif-dependent and -independent roles of AML1/Runx1 transcription factor in murine hematopoietic development. Blood, 2004; 103: 562–70.CrossRefGoogle ScholarPubMed
Levanon, D., Glusman, G., Bangsow, T., et al.Architecture and anatomy of the genomic locus encoding the human leukemia-associated transcription factor RUNX1/AML1. Gene, 2001; 262: 23–33.CrossRefGoogle ScholarPubMed
Telfer, J. C. & Rothenberg, E. V.Expression and function of a stem cell promoter for the murine CBFalpha2 gene: distinct roles and regulation in natural killer and T cell development. Dev Biol, 2001; 229: 363–82.CrossRefGoogle ScholarPubMed
Fujita, Y., Nishimura, M., Taniwaki, M., Abe, T., & Okuda, T.Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development. Biochem Biophys Res Commun, 2001; 281: 1248–55.CrossRefGoogle ScholarPubMed
Bae, S. C., Ogawa, E., Maruyama, M., et al.PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. Mol Cell Biol, 1994; 14: 3242–52.CrossRefGoogle ScholarPubMed
Levanon, D., Bernstein, Y., Negreanu, V., et al.A large variety of alternatively spliced and differentially expressed mRNAs are encoded by the human acute myeloid leukemia gene AML1. DNA Cell Biol, 1996; 15: 175–85.CrossRefGoogle ScholarPubMed
Tanaka, T., Tanaka, K., Ogawa, S., et al.An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms. EMBO J, 1995; 14: 341–50.Google ScholarPubMed
Zhang, Y. W., Bae, S. C., Huang, G., et al.A novel transcript encoding an N-terminally truncated AML1/PEBP2 alphaB protein interferes with transactivation and blocks granulocytic differentiation of 32Dcl3 myeloid cells. Mol Cell Biol, 1997; 17: 4133–45.CrossRefGoogle ScholarPubMed
Tanaka, T., Kurokawa, M., Ueki, K., et al.The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability. Mol Cell Biol, 1996; 16: 3967–79.CrossRefGoogle ScholarPubMed
Imai, Y., Kurokawa, M., Yamaguchi, Y., et al.The corepressor mSin3A regulates phosphorylation-induced activation, intranuclear location, and stability of AML1. Mol Cell Biol, 2004; 24: 1033–43.CrossRefGoogle ScholarPubMed
Okuda, T., Deursen, J., Hiebert, S. W., Grosveld, G., & Downing, J. R.AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell, 1996; 84: 321–30.CrossRefGoogle ScholarPubMed
Wang, Q., Stacy, T., Binder, M., et al.Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci U S A, 1996; 93: 3444–9.CrossRefGoogle ScholarPubMed
Wang, Q., Stacy, T., Miller, J. D., et al.The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell, 1996; 87: 697–708.CrossRefGoogle ScholarPubMed
Sasaki, K., Yagi, H., Bronson, R. T., et al.Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta. Proc Natl Acad Sci U S A, 1996; 93: 12 359–63.CrossRefGoogle ScholarPubMed
North, T., Gu, T. L., Stacy, T., et al.Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development, 1999; 126: 2563–75.Google ScholarPubMed
Tavian, M., Hallais, M. F., & Peault, B.Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo. Development, 1999; 126: 793–803.Google ScholarPubMed
Tavian, M., Coulombel, L., Luton, D., et al.Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood, 1996; 87: 67–72.Google ScholarPubMed
Garcia-Porrero, J. A., Godin, I. E., & Dieterlen-Lievre, F.Potential intraembryonic hemogenic sites at pre-liver stages in the mouse. Anat Embryol (Berl), 1995; 192: 425–35.CrossRefGoogle ScholarPubMed
Shalaby, F., Ho, J., Stanford, W. L., et al.A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell, 1997; 89: 981–90.CrossRefGoogle ScholarPubMed
Jaffredo, T., Gautier, R., Eichmann, A., & Dieterlen-Lievre, F. Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development, 1998; 125: 4575–83.Google Scholar
North, T., Gu, T. L., Stacy, T., et al.CBFA2 is required for the emergence of definitive hematopoietic cells from hemogenic endothelium [abstract]. Blood, 1998; 92: 570a.Google Scholar
Kundu, M., Chen, A., Anderson, S., et al.Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11. Blood, 2002; 100: 2449–56.CrossRefGoogle ScholarPubMed
Ichikawa, M., Asai, T., Saito, T., et al.AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med, 2004; 10: 299–304.CrossRefGoogle Scholar
Taniuchi, I., Osato, M., Egawa, T., et al.Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell, 2002; 111: 621–33.CrossRefGoogle ScholarPubMed
Nakashima, K. & de Crombrugghe, B.Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet, 2003; 19: 458–66.CrossRefGoogle ScholarPubMed
Miller, J., Horner, A., Stacy, T., et al.The core-binding factor beta subunit is required for bone formation and hematopoietic maturation. Nat Genet, 2002; 32: 645–9.CrossRefGoogle ScholarPubMed
Yoshida, C. A., Furuichi, T., Fujita, T., et al.Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet, 2002; 32: 633–8.CrossRefGoogle ScholarPubMed
Kundu, M., Javed, A., Jeon, J. P., et al.Cbfbeta interacts with Runx2 and has a critical role in bone development. Nat Genet, 2002; 32: 639–44.CrossRefGoogle Scholar
Inoue, K., Ozaki, S., Shiga, T., et al.Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nat Neurosci, 2002; 5: 946–54.CrossRefGoogle ScholarPubMed
Levanon, D., Bettoun, D., Harris-Cerruti, C., et al.The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J, 2002; 21: 3454–63.CrossRefGoogle ScholarPubMed
Li, Q. L., Ito, K., Sakakura, C., et al.Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell, 2002; 109: 113–24.CrossRefGoogle ScholarPubMed
Woolf, E., Xiao, C., Fainaru, O., et al.Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci U S A, 2003; 100: 7731–6.CrossRefGoogle ScholarPubMed
Raimondi, S. C., Kalwinsky, D. K., Hayashi, Y., et al.Cytogenetics of childhood acute nonlymphocytic leukemia. Cancer Genet Cytogenet, 1989; 40: 13–27.CrossRefGoogle ScholarPubMed
Arthur, D. C. & Bloomfield, C. D.Partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute nonlymphocytic leukemia, a new association. Blood, 1983; 61: 994–8.Google Scholar
Le Beau, M. M., Larson, R. A., Bitter, M. A., et al.Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia: a unique cytogenetic-clinical pathological association. N Engl J Med, 1998; 309: 630–6.CrossRefGoogle Scholar
Shurtleff, S. A., Meyers, S., Hiebert, S. W., et al.Heterogeneity in CBFbeta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogen ous leukemia. Blood, 1995; 85: 3695–703.Google Scholar
Costello, R., Sainty, D., Lecine, P., et al.Detection of CBFbeta/MYH11 fusion transcripts in acute myeloid leukemia: heterogeneity of cytological and molecular characteristics. Leukemia, 1997; 11: 644–50.CrossRefGoogle ScholarPubMed
Hajra, A., Liu, P. P., Wang, Q., et al.The leukemic core binding factor β-smooth muscle myosin heavy chain (CBFβ-SMMHC) chimeric protein requires both CBFβ and myosin heavy chain domains for transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A, 1995; 92: 1926–30.CrossRefGoogle Scholar
Viswanatha, D. S., Chen, I., Liu, P. P., et al.Characterization and use of an antibody detecting the CBFbeta-SMMHC fusion protein in inv(16)/t(16;16)-associated acute myeloid leukemias. Blood, 1998; 91: 1882–90.Google Scholar
Adya, N., Stacy, T., Speck, N. A., & Liu, P. P.The leukemic protein core binding factor β (CBFβ)-smooth-muscle myosin heavy chain sequesters CBFα2 into cytoskeletal filaments and aggregates. Mol Cell Biol, 1998; 18: 7432–43.CrossRefGoogle ScholarPubMed
Kanno, Y., Kanno, T., Sakakura, C., Bae, S. C., & Ito, Y.Cytoplasmic sequestration of the polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor α(CBFα) subunit by the leukemia-related PEBP2/CBFβ-SMMHC fusion protein inhibits PEBP2/CBF-mediated transactivation. Mol Cell Biol, 1998; 18: 4252–61.CrossRefGoogle ScholarPubMed
Lutterbach, B., Hou, Y., Durst, K. L., & Hiebert, S. W.The inv(16) encodes an acute myeloid leukemia 1 transcriptional corepressor. Proc Natl Acad Sci U S A, 1999; 96: 12 822–7.CrossRefGoogle ScholarPubMed
Durst, K. L., Lutterbach, B., Kummalue, T., Friedman, A. D., & Hiebert, S. W.The inv(16) fusion protein associates with co repressors via a smooth muscle myosin heavy-chain domain. Mol Cell Biol, 2003; 23: 607–19.CrossRefGoogle Scholar
Lukasik, S. M., Zhang, L., Corpora, T., et al.Altered affinity of CBF beta-SMMHC for Runx1 explains its role in leukemogenesis. Nat Struct Biol, 2002; 9: 674–9.CrossRefGoogle ScholarPubMed
Castilla, L. H., Wijmenga, C., Wang, Q., et al.Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell, 1996; 87: 687–96.CrossRefGoogle ScholarPubMed
Kogan, S. C., Lagasse, E., Atwater, S., et al.The PEBP2betaMYH11 fusion created by Inv(16)(p13;q22) in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia. Proc Natl Acad Sci U S A, 1998; 95: 11 863–8.CrossRefGoogle ScholarPubMed
Castilla, L. H., Garrett, L., Adya, N., et al.The fusion gene cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia. Nat Genet, 1999; 23: 144–6.CrossRefGoogle ScholarPubMed
Kundu, M. & Liu, P. P.Function of the inv(16) fusion gene CBFB-MYH11. Curr Opin Hematol, 2001; 8: 201–5.CrossRefGoogle ScholarPubMed
Trujillo, J. M., Cork, A., Ahearn, M. J., Youness, E. L., & McCredie, K. B.Hematologic and cytologic characterization of 8/21 translocation acute granulocytic leukemia. Blood, 1979; 53: 695–706.Google ScholarPubMed
Langabeer, S. E., Walker, H., Rogers, J. R., et al.Incidence of AML1/ETO fusion transcripts in patients entered into the MRC AML trials. MRC Adult Leukaemia Working Party. Br J Haematol, 1997; 99: 925–8.CrossRefGoogle ScholarPubMed
Gamou, T., Kitamura, E., Hosoda, F., et al.The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8 (ETO) family. Blood, 1998; 91: 4028–37.Google Scholar
Calabi, F., Pannell, R., & Pavloska, G.Gene targeting reveals a crucial role for MTG8 in the gut. Mol Cell Biol, 2001; 21: 5658–66.CrossRefGoogle Scholar
Kitabayashi, I., Ida, K., Morohoshi, F., et al.The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1. Mol Cell Biol, 1998; 18: 846–58.CrossRefGoogle ScholarPubMed
Frank, R., Zhang, J., Uchida, H., et al.The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene, 1995; 11: 2667–74.Google ScholarPubMed
Rhoades, K. L., Hetherington, C. J., Rowley, J. D., et al.Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc Natl Acad Sci U S A, 1996; 93: 11 895–900.CrossRefGoogle Scholar
Westendorf, J. J., Yamamoto, C. M., Lenny, N., et al.The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol, 1998; 18: 322–33.CrossRefGoogle Scholar
Lutterbach, B., Sun, D., Schuetz, J., & Hiebert, S. W.The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol Cell Biol, 1998; 18: 3604–11.CrossRefGoogle Scholar
Lenny, N., Meyers, S., & Hiebert, S. W.Functional domains of the t(8;21) fusion protein, AML-1/ETO. Oncogene, 1995; 11: 1761–9.Google Scholar
Wang, J., Hoshino, T., Redner, R. L., Kajigaya, S., & Liu, J. M.ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc Natl Acad Sci U S A, 1998; 95: 10 860–5.CrossRefGoogle Scholar
Zhang, J., Hug, B. A., Huang, E. Y., et al.Oligomerization of ETO is obligatory for corepressor interaction. Mol Cell Biol, 2001; 21: 156–63.CrossRefGoogle ScholarPubMed
Yergeau, D. A., Hetherington, C. J., Wang, Q., et al.Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet, 1997; 15: 303–6.CrossRefGoogle ScholarPubMed
Okuda, T., Cai, Z., Yang, S., et al.Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood, 1998; 91: 3134–43.Google ScholarPubMed
Okuda, T., Takeda, K., Fujita, Y., et al.Biological characteristics of the leukemia-associated transcriptional factor AML1 disclosed by hematopoietic rescue of AML1-deficient embryonic stem cells by using a knock-in strategy. Mol Cell Biol, 2000; 20: 319–28.CrossRefGoogle ScholarPubMed
Rhoades, K. L., Hetherington, C. J., Harakawa, N., et al.Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood, 2000; 96: 2108–15.Google ScholarPubMed
Sakakura, C., Yamaguchi-Iwai, Y., Satake, M., et al.Growth inhibition and induction of differentiation of t(8;21) acute myeloid leukemia cells by the DNA-binding domain of PEBP2 and the AML1/MTG8(ETO)-specific antisense oligonucleotide. Proc Natl Acad Sci U S A, 1994; 91: 11723–7.CrossRefGoogle Scholar
De Guzman, C. G., Warren, A. J., Zhang, Z., et al.Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol Cell Biol, 2002; 22: 5506–17.CrossRefGoogle Scholar
Mulloy, J. C., Cammenga, J., MacKenzie, K. L., et al.The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells. Blood, 2002; 99: 15–23.CrossRefGoogle ScholarPubMed
Wiemels, J. L., Xiao, Z., Buffler, P. A., et al.In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood, 2002; 99: 3801–5.CrossRefGoogle Scholar
Miyamoto, T., Nagafuji, K., Akashi, K., et al.Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia. Blood, 1996; 87: 4789–96.Google Scholar
Miyamoto, T., Weissman, I. L., & Akashi, K.AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci U S A, 2000; 97: 7521–6.CrossRefGoogle ScholarPubMed
Linggi, B., Muller-Tidow, C., Locht, L., et al.The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat Med, 2002; 8: 743–50.CrossRefGoogle Scholar
Lowe, S. W. & Sherr, C. J.Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev, 2003; 13: 77–83.CrossRefGoogle ScholarPubMed
Higuchi, M., O'Brien, D., Kumaravelu, P., et al.Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell, 2002; 1: 63–74.CrossRefGoogle Scholar
Yuan, Y., Zhou, L., Miyamoto, T., et al.AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc Natl Acad Sci U S A, 2001; 98: 10 398–403.CrossRefGoogle ScholarPubMed
Nucifora, G. & Rowley, J. D.AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood, 1995; 86: 1–14.Google ScholarPubMed
Golub, T. R., Barker, G. F., Bohlander, S. K., et al.Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A, 1995; 92: 4917–21.CrossRefGoogle ScholarPubMed
Shurtleff, S. A., Buijs, A., Behm, F. G., et al.TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia, 1995; 9: 1985–9.Google Scholar
Rubnitz, J. E., Downing, J. R., Pui, C. H., et al.TEL gene re arrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol, 1997; 15: 1150–7.CrossRefGoogle ScholarPubMed
Hiebert, S. W., Sun, W., Davis, J. N., et al.The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol Cell Biol, 1996; 16: 1349–55.CrossRefGoogle Scholar
Morrow, M., Horton, S., Kioussis, D., Brady, H. J., & Williams, O.TEL-AML1 promotes development of specific hematopoietic lineages consistent with preleukemic activity. Blood, 2004; 103: 3890–6.CrossRefGoogle ScholarPubMed
Tsuzuki, S., Seto, M., Greaves, M., & Enver, T.Modeling first-hit functions of the t(12;21) TEL-AML1 translocation in mice. Proc Natl Acad Sci U S A, 2004; 101: 8443–8.CrossRefGoogle Scholar
Imai, Y., Kurokawa, M., Izutsu, K., et al.Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis. Blood, 2000; 96: 3154–60.Google ScholarPubMed
Osato, M., Asou, N., Abdalla, E., et al.Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. Blood, 1999; 93: 1817–24.Google ScholarPubMed
Preudhomme, C., Warot-Loze, D., Roumier, C., et al.High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in M0 acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21. Blood, 2000; 96: 2862–9.Google Scholar
Tahirov, T. H., Inoue-Bungo, T., Morii, H., et al.Structural ana lyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Cell, 2001; 104: 755–67.CrossRefGoogle Scholar
Bravo, J., Li, Z., Speck, N. A., & Warren, A. J.The leukemia-associated AML1 (Runx1)–CBF beta complex functions as a DNA-induced molecular clamp. Nat Struct Biol, 2001; 8: 371–8.CrossRefGoogle ScholarPubMed
Arepally, G., Rebbeck, T. R., Song, W., et al.Evidence for genetic homogeneity in a familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML). Blood, 1998; 92: 2600–2.Google Scholar
Dowton, S. B., Beardsley, D., Jamison, D., Blattner, S., & Li, F. P.Studies of a familial platelet disorder. Blood, 1985; 65: 557–63.Google ScholarPubMed
Ho, C. Y., Otterud, B., Legare, R. D., et al.Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1–22.2. Blood, 1996; 87: 5218–24.Google ScholarPubMed
Luddy, R. E., Champion, L. A., & Schwartz, A. D.A fatal myeloproliferative syndrome in a family with thrombocytopenia and platelet dysfunction. Cancer, 1978; 41: 1959–63.3.0.CO;2-8>CrossRefGoogle Scholar
Song, W. J., Sullivan, M. G., Legare, R. D., et al.Haplo insufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet, 1999; 23: 166–75.CrossRefGoogle Scholar
Speck, N. A. & Gilliland, D. G.Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer, 2002; 2: 502–13.CrossRefGoogle ScholarPubMed
Gilliland, D. G. & Griffin, J. D.The roles of FLT3 in hematopoiesis and leukemia. Blood, 2002; 100: 1532–42.CrossRefGoogle ScholarPubMed
Fenski, R., Flesch, K., Serve, S., et al.Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br J Haematol, 2000; 108: 322–30.CrossRefGoogle ScholarPubMed
Hayakawa, F., Towatari, M., Kiyoi, H., et al.Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene, 2000; 19: 624–31.CrossRefGoogle ScholarPubMed
Kelly, L. M., Liu, Q., Kutok, J. L., et al.FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood, 2002; 99: 310–8.CrossRefGoogle Scholar
Kottaridis, P. D., Gale, R. E., Frew, M. E., et al.The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood, 2001; 98: 1752–9.CrossRefGoogle ScholarPubMed
Schnittger, S., Schoch, C., Dugas, M., et al.Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood, 2002; 100: 59–66.CrossRefGoogle ScholarPubMed
Iwai, T., Yokota, S., Nakao, M., et al.Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan. Leukemia, 1999; 13: 38–43.CrossRefGoogle ScholarPubMed
Kondo, M., Horibe, K., Takahashi, Y., et al.Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. Med Pediatr Oncol, 1999; 33: 525–9.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Xu, F., Taki, T., Yang, H. W., et al.Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol, 1999; 105: 155–62.CrossRefGoogle ScholarPubMed
Meshinchi, S., Woods, W. G., Stirewalt, D. L., et al.Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood, 2001; 97: 89–94.CrossRefGoogle ScholarPubMed
Heinrich, M. C., Blanke, C. D., Druker, B. J., & Corless, C. L.Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol, 2002; 20: 1692–703.CrossRefGoogle ScholarPubMed
Care, R. S., Valk, P. J., Goodeve, A. C., et al.Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol, 2003; 121: 775–7.CrossRefGoogle ScholarPubMed
Meshinchi, S., Stirewalt, D. L., Alonzo, T. A., et al.Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia. Blood, 2003; 102: 1474–9.CrossRefGoogle ScholarPubMed
Beghini, A., Peterlongo, P., Ripamonti, C. B., et al.C-kit mutations in core binding factor leukemias [letter]. Blood, 2000; 95: 726–7.Google Scholar
Le, D. T. & Shannon, K. M.Ras processing as a therapeutic target in hematologic malignancies. Curr Opin Hematol, 2002; 9: 308–15.CrossRefGoogle ScholarPubMed
Vogelstein, B., Civin, C. I., Preisinger, A. C., et al.RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study. Genes Chromosomes Cancer, 1990; 2: 159–62.CrossRefGoogle ScholarPubMed
Sun, W., Yeoh, E. J., Williams, W. K., Shurtleff, S. A., & Downing, J. R.Pediatric core binding factor acute myeloid leukemias contain a high frequency of RAS activating mutations [abstract]. Blood, 2002; 100: 33a.Google Scholar
Castilla, L. H., Perrat, P., Martinez, N. J., et al.Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia. Proc Natl Acad Sci U S A, 2004; 101: 4924–9.CrossRefGoogle ScholarPubMed
Raimondi, S. C., Peiper, S. C., Kitchingman, G. R., et al.Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood, 1989; 73: 1627–34.Google ScholarPubMed
Pui, C. H., Behm, F. G., Raimondi, S. C., et al.Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med, 1989; 321: 136–42.CrossRefGoogle ScholarPubMed
Pui, C. H., Ribeiro, R. C., Hancock, M. L., et al.Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N Engl J Med, 1991; 325: 1682–7.CrossRefGoogle ScholarPubMed
Pui, C. H., Frankel, L. S., Carroll, A. J., et al.Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood, 1991; 77: 440–7.Google Scholar
Kaneko, Y., Maseki, N., Takasaki, N., et al.Clinical and hematologic characteristics in acute leukemia with 11q23 translocations. Blood, 1986; 67: 484–91.Google ScholarPubMed
Rowley, J. D., Diaz, M. O., Espinosa, R., et al.Mapping chromosome bank 11q23 in human acute leukemia with biotinylated probes; identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Proc Natl Acad Sci U S A, 1990; 87: 9358–62.CrossRefGoogle Scholar
Ziemin-van der Poel, S., McCabe, N. R., Gill, H. J., et al.Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias [published erratum appears in Proc Natl Acad Sci U S A, 1992; 89: 4220]. Proc Natl Acad Sci U S A, 1991; 88: 10 735–9.CrossRefGoogle Scholar
Cimino, G., Moir, D. T., Canaani, O., et al.Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res, 1991; 51: 6712–14.Google Scholar
Tkachuk, D. C., Kohler, S., & Cleary, M. L.Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell, 1992; 71: 691–700.CrossRefGoogle ScholarPubMed
Gu, Y., Nakamura, T., Alder, H., et al.The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell, 1992; 71: 701–8.CrossRefGoogle Scholar
McCabe, N. R., Burnett, R. C., Gill, H. J., et al.Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations. Proc Natl Acad Sci U S A, 1992; 89: 11 794–8.CrossRefGoogle ScholarPubMed
Ayton, P. M. & Cleary, M. L.Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene, 2001; 20: 5695–707.CrossRefGoogle ScholarPubMed
Scandura, J. M., Boccuni, P., Cammenga, J., & Nimer, S. D.Transcription factor fusions in acute leukemia: variations on a theme. Oncogene, 2002; 21: 3422–44.CrossRefGoogle ScholarPubMed
Collins, E. C. & Rabbitts, T. H.The promiscuous MLL gene links chromosomal translocations to cellular differentiation and tumour tropism. Trends Mol Med, 2002; 8: 436–42.CrossRefGoogle ScholarPubMed
Downing, J. R. & Look, A. T.MLL fusion genes in the 11q23 acute leukemias. Cancer Treat Res, 1996; 84: 73–92.CrossRefGoogle ScholarPubMed
Waring, P. M. & Cleary, M. L.Disruption of a homolog of trithorax by 11q23 translocations: leukemogenic and transcriptional implications. Curr Top Microbiol Immunol, 1997; 220: 1–23.Google ScholarPubMed
Rubnitz, J. E., Behm, F. G., & Downing, J. R.11q23 rearrangements in acute leukemia. Leukemia, 1996; 10: 74–82.Google ScholarPubMed
Schichman, S. A., Caligiuri, M. A., Strout, M. P., et al.ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements. Cancer Res, 1994; 54: 4277–80.Google ScholarPubMed
Ingham, P. W.Genetic control of the spatial pattern of selector gene expression in Drosophila. Cold Spring Harb Symp Quant Biol, 1985; 50: 201–8.CrossRefGoogle ScholarPubMed
Mazo, A. M., Huang, D. H., Mozer, B. A., & Dawid, I. B.The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. Proc Natl Acad Sci U S A, 1990; 87: 2112–16.CrossRefGoogle ScholarPubMed
Jones, R. S. & Gelbart, W. M.The Drosophila Polycomb-group gene enhancer of zeste contains a region with sequence similarity to trithorax. Mol Cell Biol, 1993; 13: 6357–66.CrossRefGoogle ScholarPubMed
Ma, Q., Alder, H., Nelson, K. K., et al.Analysis of the murine ALL-1 gene reveals conserved domains with human ALL-1 and identified a motif shared with DNA methyltransferases. Proc Natl Acad Sci U S A, 1993; 90: 6350–4.CrossRefGoogle ScholarPubMed
Zeleznik-Le, N. J., Harden, A. M., & Rowley, J. D.11q23 translocations split the “AT-hook” cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci U S A, 1994; 91: 10610–4.CrossRefGoogle ScholarPubMed
Broeker, P. L., Harden, A., Rowley, J. D., & Zeleznik-Le, N.The mixed lineage leukemia (MLL) protein involved in 11q23 translocations contains a domain that binds cruciform DNA and scaffold attachment region (SAR) DNA. Curr Top Microbiol Immunol, 1996; 211: 259–68.Google ScholarPubMed
Hsieh, J. J., Ernst, P., Erdjument-Bromage, H., Tempst, P., & Korsmeyer, S. J.Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization. Mol Cell Biol, 2003; 23: 186–94.CrossRefGoogle ScholarPubMed
Yokoyama, A., Kitabayashi, I., Ayton, P. M., Cleary, M. L., & Ohki, M.Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties. Blood, 2002; 100: 3710–8.CrossRefGoogle ScholarPubMed
Hsieh, J. J., Cheng, E. H., & Korsmeyer, S. J.Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell, 2003; 115: 293–303.CrossRefGoogle ScholarPubMed
Yu, B. D., Hess, J. L., Horning, S. E., Brown, G. A., & Korsmeyer, S. J.Altered Hox expression and segmental identity in Mll-mutant mice. Nature, 1995; 378: 505–8.CrossRefGoogle ScholarPubMed
Hess, J. L., Yu, B. D., Li, B., Hanson, R., & Korsmeyer, S. J.Defects in yolk sac hematopoiesis in Mll-null embryos. Blood, 1997; 90: 1799–1806.Google ScholarPubMed
Simon, J.Locking in stable states of gene expression: transcriptional control during Drosophila development. Curr Opin Cell Biol, 1995; 7: 376–85.CrossRefGoogle ScholarPubMed
Schumacher, A. & Magnuson, T.Murine Polycomb- and trithorax-group genes regulate homeotic pathways and beyond. Trends Genet, 1997; 13: 167–70.CrossRefGoogle ScholarPubMed
Lugt, N. M. T., Domen, J., Linders, K., et al.Pos terior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev, 1994; 8: 757–69.CrossRefGoogle Scholar
Kanno, M., Hasegawa, M., Ishida, A., Isono, K., & Taniguchi, M.mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity. EMBO J, 1995; 14: 5672–8.Google ScholarPubMed
Akasaka, T., Kanno, M., Balling, R., et al.A role for mel-18, a Polycomb group-related vertebrate gene, during the anteropos terior specification of the axial skeleton. Development, 1996; 122: 1513–22.Google Scholar
Core, N., Bel, S., Gaunt, S. J., et al.Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice. Development, 1997; 123: 721–9.Google Scholar
Lessard, J., Baban, S., & Sauvageau, G.Stage-specific expression of Polycomb group genes in human bone marrow cells. Blood, 1998; 91: 1216–24.Google ScholarPubMed
Ernst, P., Fisher, J. K., Avery, W., et al.Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell, 2004; 6: 437–43.CrossRefGoogle ScholarPubMed
Rozenblatt-Rosen, O., Rozovskaia, T., Burakov, D., et al.The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proc Natl Acad Sci U S A, 1998; 95: 4152–7.CrossRefGoogle ScholarPubMed
Milne, T. A., Briggs, S. D., Brock, H. W., et al.MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell, 2002; 10: 1107–17.CrossRefGoogle ScholarPubMed
Lachner, M. & Jenuwein, T.The many faces of histone lysine methylation. Curr Opin Cell Biol, 2002; 14: 286–98.CrossRefGoogle ScholarPubMed
Xia, Z. B., Anderson, M., Diaz, M. O., & Zeleznik, L.MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci U S A, 2003; 100: 8342–7.CrossRefGoogle ScholarPubMed
Thirman, M. J., Levitan, D. A., Kobayashi, H., Simon, M. C., & Rowley, J. D.Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. Proc Natl Acad Sci U S A, 1994; 91: 12 110–14.CrossRefGoogle Scholar
Mitani, K., Kanda, Y., Ogawa, S., et al.Cloning of several species of MLL/MEN chimeric cDNAs in myeloid leukemia with t(11;19)(q23;p13.1) translocation. Blood, 1995; 85: 2017–24.Google Scholar
Nakamura, T., Alder, H., Gu, Y., et al.Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci U S A, 1993; 90: 4631–5.CrossRefGoogle ScholarPubMed
Rubnitz, J. E., Morrissey, J., Savage, P. A., & Cleary, M. L.ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells. Blood, 1994; 84: 1747–52.Google Scholar
Rubnitz, J. E., Behm, F. G., Curcio-Brint, A. M., et al.Molecular analysis of t(11;19) breakpoints in childhood acute leukemias. Blood, 1996; 87: 4804–8.Google Scholar
Shilatifard, A., Lane, W. S., Jackson, K. W., & Conaway, R. C., & Conaway, J. W.An RNA polymerase II elongation factor encoded by the human ELL gene. Science, 1996; 271: 1873–6.CrossRefGoogle ScholarPubMed
Shilatifard, A., Haque, D., Conaway, R. C., & Conaway, J. W.Structure and function of RNA polymerase II elongation factor ELL. Identification of two overlapping ELL functional domains that govern its interaction with polymerase and the ternary elongation complex. J Biol Chem, 1997; 272: 22 355–63.CrossRefGoogle ScholarPubMed
Bernard, O. A., Mauchauffe, M., Mecucci, C., Berghe, H., Berger, R.A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene, 1994; 9: 1039–45.Google Scholar
Hillion, J., Le Coniat, M., Jonveaux, P., Berger, R., & Bernard, O. A.AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood, 1997; 90: 3714–9.Google Scholar
Borkhardt, A., Repp, R., Haas, O. A., et al.Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene, 1997; 14: 195–202.CrossRefGoogle Scholar
Barr, F. G.Fusions involving paired box and fork head family transcription factors in the pediatric cancer alveolar rhabdomyosarcoma. Curr Top Microbiol Immunol, 1997; 220: 113–29.Google ScholarPubMed
Galili, N., Davis, R. J., Fredericks, W. J., et al.Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet, 1993; 5: 230–5.CrossRefGoogle ScholarPubMed
Shapiro, D. N., Sublett, J. E., Li, B., Downing, J. R., & Naeve, C. W.Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res, 1993; 53: 5108–12.Google ScholarPubMed
Bennicelli, J. L., Edwards, R. H., & Barr, F. G.Mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma. Proc Natl Acad Sci U S A, 1996; 93: 5455–9.CrossRefGoogle ScholarPubMed
Hjorth-Sorensen, B., Pallisgaard, N., Gronholm, M., et al.A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method. Leukemia, 1997; 11: 1588–93.CrossRefGoogle Scholar
Beverloo, H. B., Le Coniat, M., Wijsman, J., et al.Breakpoint heterogeneity in t(10;11) translocation in AML-M4/M5 resulting in fusion of AF10 and MLL is resolved by fluorescent in situ hybridization analysis. Cancer Res, 1995; 55: 4220–4.Google Scholar
Prasad, R., Leshkowitz, D., Gu, Y., et al.Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia. Proc Natl Acad Sci U S A, 1994; 91: 8107–11.CrossRefGoogle Scholar
Rowley, J. D., Reshmi, S., Sobulo, O., et al.All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood, 1997; 90: 535–41.Google Scholar
Satake, N., Ishida, Y., Otoh, Y., et al.Novel MLL-CBP fusion transcript in therapy-related chronic myelomonocytic leukemia with a t(11;16)(q23;p13) chromosome translocation. Genes Chromosomes Cancer, 1997; 20: 60–3.3.0.CO;2-7>CrossRefGoogle Scholar
Sobulo, O. M., Borrow, J., Tomek, R., et al.MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Proc Natl Acad Sci U S A, 1997; 94: 8732–7.CrossRefGoogle Scholar
Taki, T., Sako, M., Tsuchida, M., & Hayashi, Y.The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene. Blood, 1997; 89: 3945–50.Google Scholar
Ida, K., Kitabayashi, I., Taki, T., et al.Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13). Blood, 1997; 90: 4699–704.Google Scholar
Borrow, J., Stanton, V. P. J., Andresen, J. M., et al.The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet, 1996; 14: 33–41.CrossRefGoogle Scholar
Joh, T., Yamamoto, K., Kagami, Y., et al.Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus. Oncogene, 1997; 15: 1681–7.CrossRefGoogle Scholar
Tse, W., Zhu, W., Chen, H. S., & Cohen, A.A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells. Blood, 1995; 85: 650–6.Google Scholar
Corral, J., Lavenir, I., Impey, H., et al.An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell, 1996; 85: 853–61.CrossRefGoogle ScholarPubMed
Lavau, C., Szilvassy, S. J., Slany, R., & Cleary, M. L.Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J, 1997; 16: 4226–37.CrossRefGoogle ScholarPubMed
Slany, R. K., Lavau, C., & Cleary, M. L.The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol Cell Biol, 1998; 18: 122–9.CrossRefGoogle ScholarPubMed
So, C. W., Karsunky, H., Passegue, E., et al.MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell, 2003; 3: 161–71.CrossRefGoogle ScholarPubMed
Zeisig, B. B., Garcia-Cuellar, M. P., Winkler, T. H., & Slany, R. K.The oncoprotein MLL-ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell. Oncogene, 2003; 22: 1629–37.CrossRefGoogle ScholarPubMed
So, C. W., Lin, M., Ayton, P. M., Chen, E. H., & Cleary, M. L.Dimerization contributes to oncogenic activation of MLL chimeras in acute leukemias. Cancer Cell, 2003; 4: 99–110.CrossRefGoogle ScholarPubMed
Eguchi, M., Eguchi-Ishimae, M., & Greaves, M.The small oligomerization domain of gephyrin converts MLL to an oncogene. Blood, 2004; 103: 3876–82.CrossRefGoogle Scholar
Martin, M. E., Milne, T. A., Bloyer, S., et al.Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer Cell, 2003; 4: 197–207.CrossRefGoogle ScholarPubMed
Dobson, C. L., Warren, A. J., Pannell, R., Forster, A., & Rabbitts, T. H.Tumorigenesis in mice with a fusion of the leukaemia oncogene Mll and the bacterial lacZ gene. EMBO J, 2000; 19: 843–51.CrossRefGoogle ScholarPubMed
Hsu, K. & Look, A. T.Turning on a dimer: new insights into MLL chimeras. Cancer Cell, 2003; 4: 81–3.CrossRefGoogle ScholarPubMed
Yamamoto, K., Hamaguchi, H., Nagata, K., Kobayashi, M., & Taniwaki, M.Tandem duplication of the MLL gene in myelodysplastic syndrome- derived overt leukemia with trisomy 11. Am J Hematol, 1997; 55: 41–5.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Kwong, Y. L.Partial duplication of the MLL gene in acute myelogenous leukemia without karyotypic aberration. Cancer Genet Cytogenet, 1997; 97: 20–4.CrossRefGoogle ScholarPubMed
Yu, M., Honoki, K., Andersen, J., et al.MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype. Leukemia, 1996; 10: 774–80.Google ScholarPubMed
Park, I. K., He, Y., Lin, F., et al.Differential gene expression profiling of adult murine hematopoietic stem cells. Blood, 2002; 99: 488–98.CrossRefGoogle ScholarPubMed
Pineault, N., Helgason, C. D., Lawrence, H. J., & Humphries, R. K.Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp Hematol, 2002; 30: 49–57.CrossRefGoogle ScholarPubMed
Akashi, K., He, X., Chen, J., et al.Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood, 2003; 101: 383–9.CrossRefGoogle ScholarPubMed
So, C. W., Karsunky, H., Wong, P., Weissman, I. L., & Cleary, M. L.Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood, 2004; 103: 3192–9.CrossRefGoogle ScholarPubMed
Sauvageau, G., Thorsteinsdottir, U., Hough, M. R., et al.Overexpression of HOXB3 in hematopoietic cells causes defective lymphoid development and progressive myeloproliferation. Immunity, 1997; 6: 13–22.CrossRefGoogle ScholarPubMed
Sauvageau, G., Thorsteinsdottir, U., Eaves, C. J., et al.Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev, 1995; 9: 1753–65.CrossRefGoogle ScholarPubMed
Perkins, A., Kongsuwan, K., Visvader, J., Adams, J. M., & Cory, S.Homeobox gene expression plus autocrine growth factor production elicits myeloid leukemia. Proc Natl Acad Sci U S A, 1990; 87: 8398–402.CrossRefGoogle ScholarPubMed
Blatt, C., Aberdam, D., Schwartz, R., & Sachs, L.DNA rearrangement of a homeobox gene in myeloid leukaemic cells. EMBO J, 1988; 7: 4283–90.Google ScholarPubMed
Nakamura, T., Largaespada, D. A., Shaughnessy, J. D. J., Jenkins, N. A., & Copeland, N. G.Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias. Nat Genet, 1996; 12: 149–53.CrossRefGoogle ScholarPubMed
Kroon, E., Krosl, J., Thorsteinsdottir, U., et al.Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J, 1998; 17: 3714–25.CrossRefGoogle Scholar
Schnabel, C. A., Jacobs, Y., & Cleary, M. L.HoxA9-mediated immortalization of myeloid progenitors requires functional interactions with TALE cofactors Pbx and Meis. Oncogene, 2000; 19: 608–16.CrossRefGoogle ScholarPubMed
Calvo, K. R., Sykes, D. B., Pasillas, M., & Kamps, M. P.Hoxa9 immortalizes a granulocyte-macrophage colony-stimulating factor-dependent promyelocyte capable of biphenotypic differentiation to neutrophils or macrophages, independent of enforced meis expression. Mol Cell Biol, 2000; 20: 3274–85.CrossRefGoogle ScholarPubMed
Ayton, P. M. & Cleary, M. L.Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev, 2003; 17: 2298–307.CrossRefGoogle ScholarPubMed
Zeisig, B. B., Milne, T., Garcia-Cuellar, M. P., et al.Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol, 2004; 24: 617–28.CrossRefGoogle ScholarPubMed
Kumar, A. R., Hudson, W. A., Chen, W., et al.Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood, 2004; 103: 1823–8.CrossRefGoogle Scholar
Lange, B. J., Kobrinsky, N., Barnard, D. R., et al.Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood, 1998; 91: 608–15.Google ScholarPubMed
Athale, U. H., Razzouk, B. I., Raimondi, S. C., et al.Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience. Blood, 2001; 97: 3727–32.CrossRefGoogle ScholarPubMed
Zipursky, A., Poon, A., & Doyle, J.Leukemia in Down syndrome: a review. Pediatr Hematol Oncol, 1992; 9: 139–49.CrossRefGoogle ScholarPubMed
Lange, B.The management of neoplastic disorders of haematopoiesis in children with Down's syndrome. Br J Haematol, 2000; 110: 512–24.CrossRefGoogle ScholarPubMed
Zipursky, A.Transient leukaemia – a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol, 2003; 120: 930–8.CrossRefGoogle ScholarPubMed
Shivdasani, R. A.Molecular and transcriptional regulation of megakaryocyte differentiation. Stem Cells, 2001; 19: 397–407.CrossRefGoogle ScholarPubMed
Shivdasani, R. A., Fujiwara, Y., McDevitt, M. A., & Orkin, S. H.A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO J, 1997; 16: 3965–73.CrossRefGoogle ScholarPubMed
Ahmed, M., Sternberg, A., Hall, G., et al.Natural history of GATA1 mutations in Down syndrome. Blood, 2004; 103: 2480–9.CrossRefGoogle ScholarPubMed
Groet, J., McElwaine, S., Spinelli, M., et al.Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder. Lancet, 2003; 361: 1617–20.CrossRefGoogle ScholarPubMed
Hitzler, J. K., Cheung, J., Li, Y., Scherer, S. W., & Zipursky, A.GATA1 mutations in transient leukemia and acute megakaryo blastic leukemia of Down syndrome. Blood, 2003; 101: 4301–4.CrossRefGoogle Scholar
Rainis, L., Bercovich, D., Strehl, S., et al.Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. Blood, 2003; 102: 981–6.CrossRefGoogle ScholarPubMed
Wechsler, J., Greene, M., McDevitt, M. A., et al.Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet, 2002; 32: 148–52.CrossRefGoogle ScholarPubMed
Xu, G., Nagano, M., Kanezaki, R., et al.Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood, 2003; 102: 2960–8.CrossRefGoogle ScholarPubMed
Mundschau, G., Gurbuxani, S., Gamis, A. S., et al.Mutagenesis of GATA1 is an initiating event in Down syndrome leukemo genesis. Blood, 2003; 101: 4298–300.CrossRefGoogle Scholar
Shimada, A., Xu, G., Toki, T., et al.Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome. Blood, 2004; 103: 366.CrossRefGoogle ScholarPubMed
Chan, W. C., Carroll, A., Alvarado, C. S., et al.Acute megakaryo blastic leukemia in infants with t(1;22)(p13;q13) abnormality. Am J Clin Pathol, 1992; 98: 214–21.CrossRefGoogle Scholar
Carroll, A., Civin, C., Schneider, N., et al.The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryo blastic leukemia: a Pediatric Oncology Group Study. Blood, 1991; 78: 748–52.Google Scholar
Lion, T., Haas, O. A., Harbott, J., et al.The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children. Blood, 1992; 79: 3325–30.Google Scholar
Mercher, T., Coniat, M. B., Monni, R., et al.Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proc Natl Acad Sci U S A, 2001; 98: 5776–9.CrossRefGoogle Scholar
Ma, Z., Morris, S. W., Valentine, V., et al.Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet, 2001; 28: 220–1.CrossRefGoogle Scholar

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  • Molecular genetics of acute myeloid leukemia
    • By Robert B. Lorsbach, Assistant Member, Department of Pathology St. Jude Children's Research Hospital, St. Jude Children's Research Hospital, Memphis, TN, USA, James R. Downing, Member and Chair, Department of Pathology, Scientific Director, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.012
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  • Molecular genetics of acute myeloid leukemia
    • By Robert B. Lorsbach, Assistant Member, Department of Pathology St. Jude Children's Research Hospital, St. Jude Children's Research Hospital, Memphis, TN, USA, James R. Downing, Member and Chair, Department of Pathology, Scientific Director, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.012
Available formats
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  • Molecular genetics of acute myeloid leukemia
    • By Robert B. Lorsbach, Assistant Member, Department of Pathology St. Jude Children's Research Hospital, St. Jude Children's Research Hospital, Memphis, TN, USA, James R. Downing, Member and Chair, Department of Pathology, Scientific Director, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.012
Available formats
×