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19 - Pharmacogenetic studies in pediatric acute myeloid leukemia

from Part IV - Next-generation sequencing technology and pharmaco-genomics

Published online by Cambridge University Press:  18 December 2015

By
Neha S. Bhise ,
Lata Chauhan  and
Jatinder Kaur Lamba
Edited by
Krishnarao Appasani
Foreword by
Stephen W. Scherer  and
Peter M. Visscher
Neha S. Bhise
Affiliation:
University of Minnesota
Lata Chauhan
Affiliation:
University of Florida
Jatinder Kaur Lamba
Affiliation:
University of Florida
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Stephen W. Scherer
Affiliation:
University of Toronto
Peter M. Visscher
Affiliation:
University of Queensland
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Summary

Introduction

Acute myeloid leukemia (AML) is a clonal disorder characterized by appearance of immature, abnormal myeloid cells in bone marrow and other organs. AML accounts for around 15–20% of childhood leukemias. AML is a very heterogeneous disease with various subtypes classified based on the morphology, immunophenotype, and cytogenetics. In spite of advances in recent years, the 5-year survival rates for AML are ~68% for children younger than 15 years and ~57% for children between 15 and 19 years. The utilization of multiple clinical, cytogenetic, and other molecular features that are associated with response has helped in the identification of a patient being more or less likely to respond. Additionally, minimal residual disease (MRD after induction 1) has been identified as a powerful predictor of poor outcome. The nucleoside analog cytarabine (ara-C) has been the mainstay of AML chemotherapy for more than 40 years. However, extensive inter-patient variation in treatment response, development of resistance, and inadequate response to first-line therapy remain the major hurdles to effective chemotherapy. Patients within standard and high-risk categories often experience induction failure and have early relapse, warranting the need for better diagnostic and therapeutic strategies. One of the critical components contributing to the efficacy of the chemotherapeutic agents is variability in the expression and/or activity of genes involved in drug pharmacokinetics and pharmacodynamics. This chapter summarizes the recent advances in pediatric AML pharmacogenomics.

Pediatric acute myeloid leukemia

Leukemia is the most common cancer among children, with acute lymphocytic leukemia being the most common and AML being the second most common leukemia in children. Approximately 800 new cases of childhood AML are diagnosed in the US annually (Meshinchi and Arceci, 2007; Pui et al., 2011). AML is a clonal disorder originating from a hematopoietic stem cell or lineage-specific progenitor cells (Jordan, 2007; Lane et al., 2009). The malignant transformation of the stem or progenitor cells results in the accumulation of immature myeloid cells in the bone marrow and other organs. Prognostic factors help in strategizing the treatment regimens for patients with less or more likelihood of response. As indicated before, AML is a very heterogeneous disease with several subtypes that differ from one another in morphology, immunophenotye, and cytogenetics.

Type
Chapter
Information
Genome-Wide Association Studies
From Polymorphism to Personalized Medicine
 , pp. 281 - 296
Publisher: Cambridge University Press
Print publication year: 2016

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References

Abdel-Wahab, O., Patel, J. and Levine, R.L. (2011). Clinical implications of novel mutations in epigenetic modifiers in AML. Hematol. Oncol. Clin. North Am., 25, 1119–1133.CrossRefGoogle ScholarPubMed
Abraham, A., Varatharajan, S., Abbas, S., et al. (2012). Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia. Pharmacogenomics, 13, 269–282.CrossRefGoogle ScholarPubMed
Bacher, U., Schnittger, S. and Haferlach, T. (2010). Molecular genetics in acute myeloid leukemia. Curr. Opin. Oncol., 22, 646–655.CrossRefGoogle ScholarPubMed
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. (1976). Proposals for the classification of the acute leukaemias. French–American–British (FAB) co-operative group. Br. J. Haematol., 33, 451–458.CrossRefGoogle ScholarPubMed
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. (1980). A variant form of hypergranular promyelocytic leukaemia (M3). Br. J. Haematol., 44, 169–170.CrossRefGoogle Scholar
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. (1985a). Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French–American–British Cooperative Group. Ann. Int. Med., 103, 460–462.Google Scholar
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. (1985b). Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French–American–British Cooperative Group. Ann. Int. Med., 103, 620–625.Google ScholarPubMed
Bennett, J.M., Catovsky, D., Daniel, M.T., et al. (1991). Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO). Br. J. Haematol., 78, 325–329.CrossRefGoogle Scholar
Bhatla, D., Gerbing, R.B., Alonzo, T.A., et al. (2009). Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia. Br. J. Haematol., 144, 388–394.CrossRefGoogle ScholarPubMed
Bianchi, V., Pontis, E. and Reichard, P. (1986). Interrelations between substrate cycles and de novo synthesis of pyrimidine deoxyribonucleoside triphosphates in 3T6 cells. Proc. Natl Acad. Sci. USA, 83, 986–990.CrossRefGoogle ScholarPubMed
Bierau, J., Van Gennip, A.H., Leen, R., et al. (2003). Cyclopentenyl cytosine primes SK-N-BE(2)c neuroblastoma cells for cytarabine toxicity. Int. J. Cancer, 103, 387–392.CrossRefGoogle ScholarPubMed
Bierau, J., van Gennip, A.H., Leen, R., et al. (2006). Cyclopentenyl cytosine-induced activation of deoxycytidine kinase increases gemcitabine anabolism and cytotoxicity in neuroblastoma. Cancer Chemother. Pharmacol., 57, 105–113.CrossRefGoogle ScholarPubMed
Braunagel, D., Schaich, M., Kramer, M., et al. (2012). The T_T genotype within the NME1 promoter single nucleotide polymorphism -835 C/T is associated with an increased risk of cytarabine induced neurotoxicity in patients with acute myeloid leukemia. Leuk. Lymph., 53, 952–957.CrossRefGoogle Scholar
Cao, X., Mitra, A.K., Pounds, S., et al. (2013). RRM1 and RRM2 pharmacogenetics: association with phenotypes in HapMap cell lines and acute myeloid leukemia patients. Pharmacogenomics, 14, 1449–1466.CrossRefGoogle ScholarPubMed
Capizzi, R.L., White, J.C., Powell, B.L. and Perrino, F. (1991). Effect of dose on the pharmacokinetic and pharmacodynamic effects of cytarabine. Semin. Hematol., 28, 54–69.Google ScholarPubMed
Chabner, B.A., Hande, K.R. and Drake, J.C. (1979). Ara-C metabolism: implications for drug resistance and drug interactions. Bull. Cancer, 66, 89–92.Google ScholarPubMed
Cheson, B.D., Bennett, J.M., Kopecky, K.J., et al. (2003). Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J. Clin. Oncol., 21, 4642–4649.CrossRefGoogle Scholar
Chiba, P., Tihan, T., Szekeres, T., et al. (1990). Concordant changes of pyrimidine metabolism in blasts of two cases of acute myeloid leukemia after repeated treatment with ara-C in vivo. Leukemia, 4, 761–765.Google ScholarPubMed
Davies, S.M., Robison, L.L., Buckley, J.D., et al. (2001). Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia. J. Clin. Oncol., 19, 1279–1287.CrossRefGoogle ScholarPubMed
Dumontet, C., Fabianowska-Majewska, K., Mantincic, D., et al. (1999). Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br. J. Haematol., 106, 78–85.CrossRefGoogle ScholarPubMed
Falini, B. and Martelli, M.P. (2011). NPM1-mutated AML: targeting by disassembling. Blood, 118, 2936–2938.CrossRefGoogle ScholarPubMed
Falk, I.J., Fyrberg, A., Paul, E., et al. (2013). Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5ʹ-nucleotidase. Am. J. Hematol., 88, 1001–1006.CrossRefGoogle ScholarPubMed
Fridland, A. and Verhoef, V. (1987). Mechanism for ara-CTP catabolism in human leukemic cells and effect of deaminase inhibitors on this process. Semin. Oncol., 14, 262–268.Google ScholarPubMed
Galmarini, C.M., Cros, E., Thomas, X., Jordheim, L. and Dumontet, C. (2005). The prognostic value of cN-II and cN-III enzymes in adult acute myeloid leukemia. Haematologica, 90, 1699–1701.Google ScholarPubMed
Galmarini, C.M., Thomas, X., Calvo, F., et al. (2002a). Potential mechanisms of resistance to cytarabine in AML patients. Leuk. Res., 26, 621–629.CrossRefGoogle ScholarPubMed
Galmarini, C.M., Thomas, X., Calvo, F., et al. (2002b). In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia. Br. J. Haematol., 117, 860–868.CrossRefGoogle ScholarPubMed
Gamazon, E.R., Lamba, J.K., Pounds, S., et al. (2013). Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients. Blood, 121, 4366–4376.CrossRefGoogle Scholar
Gati, W.P., Paterson, A.R., Larratt, L.M., Turner, A.R. and Belch, A.R. (1997). Sensitivity of acute leukemia cells to cytarabine is a correlate of cellular es nucleoside transporter site content measured by flow cytometry with SAENTA-fluorescein. Blood, 90, 346–353.Google ScholarPubMed
Gati, W.P., Paterson, A.R., Belch, A.R., et al. (1998). Es nucleoside transporter content of acute leukemia cells: role in cell sensitivity to cytarabine (araC). Leuk. Lymph., 32, 45–54.Google Scholar
Gilbert, J.A., Salavaggione, O.E., Ji, Y., et al. (2006). Gemcitabine pharmacogenomics: cytidine deaminase and deoxycytidylate deaminase gene resequencing and functional genomics. Clin. Cancer Res., 12, 1794–1803.CrossRefGoogle ScholarPubMed
Grant, S. (1998). Ara-C: cellular and molecular pharmacology. Adv. Cancer Res., 72, 197–233.Google ScholarPubMed
Gu, T.L., Nardone, J., Wang, Y., et al. (2011). Survey of activated FLT3 signaling in leukemia. PloS ONE, 6, e19169.CrossRefGoogle ScholarPubMed
Hapke, D.M., Stegmann, A.P. and Mitchell, B.S. (1996). Retroviral transfer of deoxycytidine kinase into tumor cell lines enhances nucleoside toxicity. Cancer Res., 56, 2343–2347.Google ScholarPubMed
Hartford, C.M., Duan, S., Delaney, S.M., et al. (2009). Population-specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity. Blood, 113, 2145–2153.CrossRefGoogle ScholarPubMed
Hou, H.A., Lin, C.C., Chou, W.C., et al. (2014). Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia. Leukemia, 28, 50–58.CrossRefGoogle ScholarPubMed
Hunsucker, S.A., Mitchell, B.S. and Spychala, J. (2005). The 5ʹ-nucleotidases as regulators of nucleotide and drug metabolism. Pharmacol. Therapeut., 107, 1–30.CrossRefGoogle ScholarPubMed
Jahns-Streubel, G., Reuter, C., Auf der Landwehr, U., et al. (1997). Activity of thymidine kinase and of polymerase alpha as well as activity and gene expression of deoxycytidine deaminase in leukemic blasts are correlated with clinical response in the setting of granulocyte-macrophage colony-stimulating factor-based priming before and during TAD-9 induction therapy in acute myeloid leukemia. Blood, 90, 1968–1976.Google ScholarPubMed
Joerger, M., Bosch, T.M., Doodeman, V.D., et al. (2006). Novel deoxycytidine kinase gene polymorphisms: a population screening study in Caucasian healthy volunteers. Eur. J. Clin. Pharmacol., 62, 681–684.CrossRefGoogle ScholarPubMed
Jordan, C.T. (2007). The leukemic stem cell. Best Pract. Res. Clin. Haematol., 20, 13–18.CrossRefGoogle ScholarPubMed
Kakihara, T., Fukuda, T., Tanaka, A., et al. (1998). Expression of deoxycytidine kinase (dCK) gene in leukemic cells in childhood: decreased expression of dCK gene in relapsed leukemia. Leuk. Lymph., 31, 405–409.Google ScholarPubMed
Kaleem, Z. and White, G. (2001). Diagnostic criteria for minimally differentiated acute myeloid leukemia (AML-M0). Evaluation and a proposal. Am. J. Clin. Pathol., 115, 876–884.CrossRefGoogle Scholar
Kim, K.I., Huh, I.S., Kim, I.W., et al. (2013). Combined interaction of multi-locus genetic polymorphisms in cytarabine arabinoside metabolic pathway on clinical outcomes in adult acute myeloid leukaemia (AML) patients. Eur. J. Cancer, 49, 403–410.CrossRefGoogle ScholarPubMed
Kirch, H.C., Schroder, J., Hoppe, H., et al. (1998). Recombinant gene products of two natural variants of the human cytidine deaminase gene confer different deamination rates of cytarabine in vitro. Exp. Hematol., 26, 421–425.Google ScholarPubMed
Kocabas, N.A., Aksoy, P., Pelleymounter, L.L., et al. (2008). Gemcitabine pharmacogenomics: deoxycytidine kinase and cytidylate kinase gene resequencing and functional genomics. Drug Metab. Dispos., 36, 1951–1959.CrossRefGoogle ScholarPubMed
Kufe, D.W., Major, P.P., Egan, E.M. and Beardsley, G.P. (1980). Correlation of cytotoxicity with incorporation of ara-C into DNA. J. Biol. Chem., 255, 8997–9000.Google ScholarPubMed
Lamba, J.K., Crews, K., Pounds, S., t al. (2007). Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. J. Pharmacol. Exp. Therapeut., 323, 935–945.CrossRefGoogle ScholarPubMed
Lane, S.W., Scadden, D.T. and Gilliland, D.G. (2009). The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood, 114, 1150–1157.CrossRefGoogle ScholarPubMed
Li, L., Fridley, B.L., Kalari, K., et al. (2009). Gemcitabine and arabinosylcytosin pharmacogenomics: genome-wide association and drug response biomarkers. PloS ONE, 4, e7765.CrossRefGoogle ScholarPubMed
Liliemark, J.O. and Plunkett, W. (1986). Regulation of 1-beta-D-arabinofuranosylcytosine 5ʹ-triphosphate accumulation in human leukemia cells by deoxycytidine 5ʹ-triphosphate. Cancer Res., 46, 1079–1083.Google ScholarPubMed
Lotfi, K., Karlsson, K., Fyrberg, A., et al. (2006). The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia. Biochem. Pharmacol., 71, 882–890.CrossRefGoogle ScholarPubMed
Mahfouz, R.Z., Jankowska, A., Ebrahem, Q., et al. (2013). Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin. Cancer Res., 19, 938–948.CrossRefGoogle ScholarPubMed
Mahlknecht, U., Dransfeld, C.L., Bulut, N., et al. (2009). SNP analyses in cytarabine metabolizing enzymes in AML patients and their impact on treatment response and patient survival: identification of CDA SNP C-451 T as an independent prognostic parameter for survival. Leukemia, 23, 1929–1932.CrossRefGoogle Scholar
Major, P.P., Egan, E.M., Beardsley, G.P., Minden, M.D. and Kufe, D.W. (1981). Lethality of human myeloblasts correlates with the incorporation of arabinofuranosylcytosine into DNA. Proc. Natl Acad. Sci. USA, 78, 3235–3239.CrossRefGoogle ScholarPubMed
Maring, J.G., Groen, H.J., Wachters, F.M., Uges, D.R. and de Vries, E.G. (2005). Genetic factors influencing pyrimidine-antagonist chemotherapy. Pharmacogenom. J., 5, 226–243.CrossRefGoogle ScholarPubMed
Meshinchi, S. and Arceci, R.J. (2007). Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist, 12, 341–355.CrossRefGoogle ScholarPubMed
Meuth, M (1989). The molecular basis of mutations induced by deoxyribonucleoside triphosphate pool imbalances in mammalian cells. Exp. Cell Res., 181, 305–316.CrossRefGoogle ScholarPubMed
Micozzi, D., Carpi, F.M., Pucciarelli, S., et al. (2014). Human cytidine deaminase: a biochemical characterization of its naturally occurring variants. Int. J. Biol. Macromolec., 63, 64–74.Google ScholarPubMed
Mitra, A.K., Crews, K.R., Pounds, S., et al. (2011). Genetic variants in cytosolic 5ʹ-nucleotidase II are associated with its expression and cytarabine sensitivity in HapMap cell lines and in patients with acute myeloid leukemia. J. Pharmacol. Exp. Therapeut., 339, 9–23.CrossRefGoogle ScholarPubMed
Myers, S.N., Goyal, R.K., Roy, J.D., et al. (2006). Functional single nucleotide polymorphism haplotypes in the human equilibrative nucleoside transporter 1. Pharmacogenet. Genom., 16, 315–320.CrossRefGoogle ScholarPubMed
Naoe, T., Tagawa, Y., Kiyoi, H., et al. (2002). Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy. Leukemia, 16, 203–208.Google ScholarPubMed
Osato, D.H., Huang, C.C., Kawamoto, M., et al. (2003). Functional characterization in yeast of genetic variants in the human equilibrative nucleoside transporter, ENT1. Pharmacogenetics, 13, 297–301.CrossRefGoogle ScholarPubMed
Pui, C.H., Carroll, W.L., Meshinchi, S. and Arceci, R.J. (2011). Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J. Clin. Oncol., 29, 551–565.CrossRefGoogle ScholarPubMed
Rau, R. and Brown, P. (2009). Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity. Hematol. Oncol., 27, 171–181.CrossRefGoogle ScholarPubMed
Raza, A., Gezer, S., Anderson, J., et al. (1992). Relationship of [3 H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study. Exp. Hematol., 20, 1194–1200.Google Scholar
Rockova, V., Abbas, S., Wouters, B.J., et al. (2011). Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood, 118, 1069–1076.CrossRefGoogle ScholarPubMed
Rubnitz, J.E. and Inaba, H. (2012). Childhood acute myeloid leukaemia. Br. J. Haematol., 159, 259–276.CrossRefGoogle ScholarPubMed
Sallmyr, A., Fan, J., Datta, K., et al. (2008). Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML. Blood, 111, 3173–3182.CrossRefGoogle ScholarPubMed
Schroder, J.K., Kirch, C., Seeber, S. and Schutte, J. (1998a). Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia. Br. J. Haematol., 103, 1096–1103.CrossRefGoogle ScholarPubMed
Schroder, J.K., Seidelmann, M., Kirch, H.C., Seeber, S. and Schutte, J. (1998b). Assessment of resistance induction to cytosine arabinoside following transfer and overexpression of the deoxycytidylate deaminase gene in vitro. Leukemia Res., 22, 619–624.CrossRefGoogle ScholarPubMed
Shao, J., Zhou, B., Chu, B. and Yen, Y. (2006). Ribonucleotide reductase inhibitors and future drug design. Curr. Cancer Drug Targets, 6, 409–431.CrossRefGoogle ScholarPubMed
Shi, J.Y., Shi, Z.Z., Zhang, S.J., et al. (2004). Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Pharmacogenetics, 14, 759–768.CrossRefGoogle ScholarPubMed
Tasian, S.K., Pollard, J.A. and Aplenc, R. (2014a). Molecular therapeutic approaches for pediatric acute myeloid leukemia. Front. Oncol., 4, 55.CrossRefGoogle ScholarPubMed
Tasian, S.K., Teachey, D.T. and Rheingold, S.R. (2014b). Targeting the PI3 K/mTOR pathway in pediatric hematologic malignancies. Front. Oncol., 4, 108.CrossRefGoogle Scholar
Vardiman, J.W., Thiele, J., Arber, D.A., et al. (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937–951.CrossRefGoogle ScholarPubMed
Verhoef, V., Sarup, J. and Fridland, A. (1981). Identification of the mechanism of activation of 9-beta-D-arabinofuranosyladenine in human lymphoid cells using mutants deficient in nucleoside kinases. Cancer Res., 41, 4478–4483.Google ScholarPubMed
Verschuur, A.C., van Gennip, A.H., Leen, R., Voute, P.A. and van Kuilenburg, A.B. (2000). Cyclopentenyl cytosine increases the phosphorylation and incorporation into dna of arabinofuranosyl cytosine in a myeloid leukemic cell-line. Adv. Exp. Med. Biol., 486, 311–317.Google Scholar
Verschuur, A.C., Brinkman, J., Van Gennip, A.H., et al. (2001). Cyclopentenyl cytosine induces apoptosis and increases cytarabine-induced apoptosis in a T-lymphoblastic leukemic cell-line. Leukemia Res., 25, 891–900.CrossRefGoogle Scholar
Verschuur, A.C., Van Gennip, A.H., Leen, R., et al. (2002). Cyclopentenyl cytosine increases the phosphorylation and incorporation into DNA of 1-beta-D-arabinofuranosyl cytosine in a human T-lymphoblastic cell line. Int. J. Cancer, 98, 616–623.CrossRefGoogle Scholar
Voso, M.T., D'Alo, F., Putzulu, R., et al. (2002). Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Blood, 100, 2703–2707.CrossRefGoogle ScholarPubMed
Xiao, Q., Deng, D., Li, H., et al. (2014). GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis. Ann. Hematol., 93, 1381–1390.CrossRefGoogle ScholarPubMed
Xu, P.P., Chen, B.A., Feng, J.F., et al. (2012). Association of polymorphisms of cytosine arabinoside-metabolizing enzyme gene with therapeutic efficacy for acute myeloid leukemia. Chin. Med. J., 125, 2137–2143.Google ScholarPubMed
Yamauchi, T., Negoro, E., Kishi, S., et al. (2009). Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 5ʹ-nucleotidase II expression ratio in primary acute myeloid leukemia cells. Biochem. Pharmacol., 77, 1780–1786.CrossRefGoogle ScholarPubMed
Yates, J., Glidewell, O., Wiernik, P., et al. (1982). Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood, 60, 454–462.Google ScholarPubMed
Yee, S.W., Mefford, J.A., Singh, N., et al. (2013). Impact of polymorphisms in drug pathway genes on disease-free survival in adults with acute myeloid leukemia. J. Hum. Genet., 58, 353–361.CrossRefGoogle ScholarPubMed
Yue, L., Saikawa, Y., Ota, K., et al. (2003). A functional single-nucleotide polymorphism in the human cytidine deaminase gene contributing to ara-C sensitivity. Pharmacogenetics, 13, 29–38.CrossRefGoogle ScholarPubMed

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