Book contents
- Atlas of Pediatric Hematopathology
- Atlas of Pediatric Hematopathology
- Copyright page
- Contents
- Contributors
- Section I Peripheral Blood
- Section II Normal and Non-neoplastic Hematolymphoid Diseases
- Section III Mature Lymphoid Neoplasm
- Section IV Precursor Hematopoietic Neoplasms and Related Neoplasms
- Chapter 13 Precursor Lymphoblastic Leukemia/Lymphoma
- Chapter 14 Blastic Plasmacytoid Dendritic Cell Neoplasm
- Chapter 15 Acute Myeloid Leukemia and Related Precursor Neoplasms
- Chapter 16 Myeloproliferative Neoplasms
- Chapter 17 Myelodysplastic/Myeloproliferative Neoplasms
- Chapter 18 Childhood Myelodysplastic Syndrome
- Chapter 19 Germline Predisposition to Myeloid Neoplasia
- Chapter 20 Germline Predisposition to Lymphoid Neoplasm
- Chapter 21 Mastocytosis and Myeloid Lymphoid Neoplasms with Eosinophilia
- Section V Histiocytic Neoplasm and Miscellaneous Bone Marrow Diseases
- Index
- References
Chapter 19 - Germline Predisposition to Myeloid Neoplasia
from Section IV - Precursor Hematopoietic Neoplasms and Related Neoplasms
Published online by Cambridge University Press: 25 November 2023
Book contents
- Atlas of Pediatric Hematopathology
- Atlas of Pediatric Hematopathology
- Copyright page
- Contents
- Contributors
- Section I Peripheral Blood
- Section II Normal and Non-neoplastic Hematolymphoid Diseases
- Section III Mature Lymphoid Neoplasm
- Section IV Precursor Hematopoietic Neoplasms and Related Neoplasms
- Chapter 13 Precursor Lymphoblastic Leukemia/Lymphoma
- Chapter 14 Blastic Plasmacytoid Dendritic Cell Neoplasm
- Chapter 15 Acute Myeloid Leukemia and Related Precursor Neoplasms
- Chapter 16 Myeloproliferative Neoplasms
- Chapter 17 Myelodysplastic/Myeloproliferative Neoplasms
- Chapter 18 Childhood Myelodysplastic Syndrome
- Chapter 19 Germline Predisposition to Myeloid Neoplasia
- Chapter 20 Germline Predisposition to Lymphoid Neoplasm
- Chapter 21 Mastocytosis and Myeloid Lymphoid Neoplasms with Eosinophilia
- Section V Histiocytic Neoplasm and Miscellaneous Bone Marrow Diseases
- Index
- References
Summary
There is increasing recognition of the role inherited and de novo germline mutations play in the development of myeloid neoplasia [1], particularly in children, adolescents, and young/middle-aged adults [2, 3]. Germline mutation inheritance may be autosomal dominant with variable penetrance, X-linked, or autosomal recessive. Family history of neoplasia or cytopenia may be helpful in identifying potential cases with germline predisposition. However, variability in disease penetrance within family members harboring the same mutation may mask early recognition of familial disease. Additionally, patients harboring de novo germline mutations may have no family history of disease. The World Health Organization’s (WHO) 2016 classification of tumors of the hematopoietic and lymphoid tissues recognizes three major classifications of myeloid neoplasms with germline predispositions: myeloid neoplasms without preexisting disorder or organ dysfunction, myeloid neoplasms with preexisting platelet disorders, and myeloid neoplasms with other organ dysfunctions (including inherited bone marrow failure syndromes) [1].
- Type
- Chapter
- Information
- Atlas of Pediatric Hematopathology , pp. 207 - 229Publisher: Cambridge University PressPrint publication year: 2023
References
Swerdlow, SH, Campo, E, Pileri, SA, Harris, NL, Stein, H, Siebert, R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20): 2375–90.CrossRefGoogle ScholarPubMed
Babushok, DV, Bessler, M, Olson, TS. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma. 2016; 57(3): 520–36.CrossRefGoogle ScholarPubMed
Weinberg, OK, Kuo, F, Calvo, KR. Germline predisposition to hematolymphoid neoplasia. Am J Clin Pathol. 2019; 152(3): 258–76.CrossRefGoogle ScholarPubMed
Song, WJ, Sullivan, MG, Legare, RD, Hutchings, S, Tan, X, Kufrin, D, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999; 23(2): 166–75.CrossRefGoogle ScholarPubMed
Smith, ML, Cavenagh, JD, Lister, TA, Fitzgibbon, J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004; 351(23): 2403–7.CrossRefGoogle ScholarPubMed
Pabst, T, Eyholzer, M, Haefliger, S, Schardt, J, Mueller, BU. Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol. 2008; 26(31): 5088–93.CrossRefGoogle ScholarPubMed
Taskesen, E, Bullinger, L, Corbacioglu, A, Sanders, MA, Erpelinck, CA, Wouters, BJ, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: Further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011; 117(8): 2469–75.CrossRefGoogle Scholar
Tawana, K, Rio-Machin, A, Preudhomme, C, Fitzgibbon, J. Familial CEBPA-mutated acute myeloid leukemia. Semin Hematol. 2017; 54(2): 87–93.CrossRefGoogle ScholarPubMed
Maciejewski, JP, Padgett, RA, Brown, AL, Müller-Tidow, C. DDX41-related myeloid neoplasia. Semin Hematol. 2017; 54(2): 94–7.CrossRefGoogle ScholarPubMed
Lewinsohn, M, Brown, AL, Weinel, LM, Phung, C, Rafidi, G, Lee, MK, et al. Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies. Blood. 2016; 127(8): 1017–23.CrossRefGoogle ScholarPubMed
Schlegelberger, B, Heller, PG. RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM). Semin Hematol. 2017; 54(2): 75–80.CrossRefGoogle ScholarPubMed
Chisholm, KM, Denton, C, Keel, S, Geddis, AE, Xu, M, Appel, BE, et al. Bone marrow morphology associated with germline RUNX1 mutations in patients with familial platelet disorder with associated myeloid malignancy. Pediatr Dev Pathol. 2019; 22(4): 315–28.CrossRefGoogle ScholarPubMed
Kanagal-Shamanna, R, Loghavi, S, DiNardo, CD, Medeiros, LJ, Garcia-Manero, G, Jabbour, E, et al. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation. Haematologica. 2017; 102(10): 1661–70.CrossRefGoogle ScholarPubMed
Pippucci, T, Savoia, A, Perrotta, S, Pujol-Moix, N, Noris, P, Castegnaro, G, et al. Mutations in the 5’ UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. Am J Hum Genet. 2011; 88(1): 115–20.CrossRefGoogle ScholarPubMed
Hock, H, Shimamura, A. ETV6 in hematopoiesis and leukemia predisposition. Semin Hematol. 2017; 54(2): 98–104.CrossRefGoogle ScholarPubMed
Zhang, MY, Churpek, JE, Keel, SB, Walsh, T, Lee, MK, Loeb, KR, et al. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet. 2015; 47(2): 180–5.CrossRefGoogle ScholarPubMed
Spinner, MA, Sanchez, LA, Hsu, AP, Shaw, PA, Zerbe, CS, Calvo, KR, et al. GATA2 deficiency: A protean disorder of hematopoiesis, lymphatics, and immunity. Blood. 2014; 123(6): 809–21.CrossRefGoogle ScholarPubMed
Wlodarski, MW, Hirabayashi, S, Pastor, V, Starý, J, Hasle, H, Masetti, R, et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016; 127(11): 1387–97; quiz 518.CrossRefGoogle ScholarPubMed
Nováková, M, Žaliová, M, Suková, M, Wlodarski, M, Janda, A, Froňková, E, et al. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome. Haematologica. 2016; 101(6): 707–16.CrossRefGoogle ScholarPubMed
Valdez, JM, Nichols, KE, Kesserwan, C. Li-Fraumeni syndrome: A paradigm for the understanding of hereditary cancer predisposition. Br J Haematol. 2017; 176(4): 539–52.CrossRefGoogle ScholarPubMed
Dokal, I. Dyskeratosis congenita. Hematology Am Soc Hematol Educ Program. 2011; 2011: 480–6.Google ScholarPubMed
Savage, SA, Bertuch, AA. The genetics and clinical manifestations of telomere biology disorders. Genet Med. 2010; 12(12): 753–64.CrossRefGoogle ScholarPubMed
Alter, BP. Fanconi anemia and the development of leukemia. Best Pract Res Clin Haematol. 2014; 27 (3-4): 214-21.CrossRefGoogle ScholarPubMed
Burroughs, L, Woolfrey, A, Shimamura, A. Shwachman-Diamond syndrome: A review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am. 2009; 23(2): 233–48.CrossRefGoogle ScholarPubMed
Vlachos, A, Ball, S, Dahl, N, Alter, BP, Sheth, S, Ramenghi, U, et al. Diagnosing and treating Diamond Blackfan anaemia: Results of an international clinical consensus conference. Br J Haematol. 2008; 142(6): 859–76.CrossRefGoogle ScholarPubMed
Skokowa, J, Dale, DC, Touw, IP, Zeidler, C, Welte, K. Severe congenital neutropenias. Nat Rev Dis Primers. 2017; 3: 17032.CrossRefGoogle ScholarPubMed
Narumi, S, Amano, N, Ishii, T, Katsumata, N, Muroya, K, Adachi, M, et al. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat Genet. 2016; 48(7): 792–7.CrossRefGoogle Scholar
Chen, DH, Below, JE, Shimamura, A, Keel, SB, Matsushita, M, Wolff, J, et al. Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L. Am J Hum Genet. 2016; 98(6): 1146–58.CrossRefGoogle ScholarPubMed
Davidsson, J, Puschmann, A, Tedgård, U, Bryder, D, Nilsson, L, Cammenga, J. SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies. Leukemia. 2018; 32(5): 1106–15.CrossRefGoogle ScholarPubMed
Germeshausen, M, Ancliff, P, Estrada, J, Metzler, M, Ponstingl, E, Rütschle, H, et al. MECOM-associated syndrome: A heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia. Blood Adv. 2018; 2(6): 586–96.CrossRefGoogle ScholarPubMed
Ahmed, M, Sternberg, A, Hall, G, Thomas, A, Smith, O, O’Marcaigh, A, et al. Natural history of GATA1 mutations in Down syndrome. Blood. 2004; 103(7): 2480–9.CrossRefGoogle ScholarPubMed
Khan, I, Malinge, S, Crispino, J. Myeloid leukemia in Down syndrome. Crit Rev Oncog. 2011; 16 (1–2): 25–36.CrossRefGoogle ScholarPubMed
Labuhn, M, Perkins, K, Matzk, S, Varghese, L, Garnett, C, Papaemmanuil, E, et al. Mechanisms of progression of myeloid preleukemia to transformed myeloid leukemia in children with Down syndrome. Cancer Cell. 2019; 36(2): 123–38.e10.CrossRefGoogle ScholarPubMed