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Review

Recent advances in genetic predisposition to pediatric acute lymphoblastic leukemia

, , , &
Pages 55-70 | Received 01 Sep 2019, Accepted 24 Oct 2019, Published online: 19 Nov 2019

References

  • Pui CH, Yang JJ, Bhakta N, et al. Global efforts toward the cure of childhood acute lymphoblastic leukaemia. Lancet Child Adolesc Health. 2018 Jun;2(6):440–454. PubMed PMID: 30169285; PubMed Central PMCID: PMC6467529.
  • Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017 Mar 20;35(9):975–983. PubMed PMID: 28297628; PubMed Central PMCID: PMC5455679.
  • Pui CH, Nichols KE, Yang JJ. Somatic and germline genomics in paediatric acute lymphoblastic leukaemia. Nat Rev Clin Oncol. 2019 Apr;16(4):227–240. PubMed PMID: 30546053.
  • Plon SE, Lupo PJ. Genetic predisposition to childhood cancer in the genomic era. Annu Rev Genomics Hum Genet. 2019;20:241–263.
  • Scollon S, Anglin AK, Thomas M, et al. A comprehensive review of pediatric tumors and associated cancer predisposition syndromes. J Genet Couns. 2017;26(3):387–434. PubMed PMID: 28357779.
  • Adam M, Ardinger H, Pagon R, et al. Ataxia-Telangiectasia–GeneReviews®.
  • Flanagan M, Cunniff C. Bloom syndrome. Seattle: GeneReviews®[Internet]: University of Washington; 2019.
  • Mehta PA, Tolar J. Fanconi anemia. Seattle: GeneReviews®[Internet]: University of Washington; 2018.
  • Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, et al. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis. 2012;7(1):13. PubMed PMID: 22373003.
  • Anderson RC. Familial leukemia: a report of leukemia in five siblings, with a brief review of the genetic aspects of this disease. AMA Am J Dis Children. 1951;81(3):313–322. PubMed PMID: 14810167.
  • Jr CW H, Moloney WC. Familial leukemia: five cases of acute leukemia in three generations. N Engl J Med. 1965;272(17):882–887. PubMed PMID: 14274439.
  • Gunz F, Fitzgerald P, Crossen P, et al. Multiple cases of leukemia in a sibship. Blood. 1966;27(4):482–489. PubMed PMID: 5931581.
  • Blattner WA, Naiman JL, Mann DL, et al. Immunogenetic determinants of familial acute lymphocytic leukemia. Ann Intern Med. 1978;89(2):173–176. PubMed PMID: 307933.
  • Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250(4985):1233–1238.
  • Matthias P, Rolink AG. Transcriptional networks in developing and mature B cells. Nat Rev Immunol. 2005 Jun;5(6):497–508. PubMed PMID: 15928681.
  • Urbanek P, Wang ZQ, Fetka I, et al. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell. 1994 Dec 2;79(5):901–912. PubMed PMID: 8001127.
  • Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007 Apr 12;446(7137):758–764. PubMed PMID: 17344859.
  • Kuiper RP, Schoenmakers EF, van Reijmersdal SV, et al. High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression. Leukemia. 2007 Jun;21(6):1258–1266. PubMed PMID: 17443227.
  • Auer F, Ruschendorf F, Gombert M, et al. Inherited susceptibility to pre B-ALL caused by germline transmission of PAX5 c.547G>A. Leukemia. 2014;28:1136–1138. PubMed PMID: 24287434.
  • Shah S, Schrader KA, Waanders E, et al. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet. 2013;45(10):1226–1231. PubMed PMID: 24013638.
  • Rodriguez-Hernandez G, Hauer J, Martin-Lorenzo A, et al. Infection exposure promotes ETV6-RUNX1 precursor B-cell leukemia viaimpaired H3K4 demethylases. Cancer Res. 2017 Aug 15;77(16):4365–4377. PubMed PMID: 28630052.
  • Heltemes-Harris LM, Willette MJ, Ramsey LB, et al. Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia. J Exp Med. 2011;208(6):1135–1149.
  • Dang J, Wei L, de Ridder J, et al. PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia. Blood. 2015;125(23):3609–3617. PubMed PMID: 25855603.
  • Chan LN, Chen Z, Braas D, et al. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature. 2017;542(7642):479. PubMed PMID: 28192788.
  • Guidez F, Petrie K, Ford AM, et al. Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia–associated TEL-AML1 oncoprotein. Blood. 2000;96(7):2557–2561. PubMed PMID: 11001911.
  • Chakrabarti SR, Nucifora G. The leukemia-associated gene TEL encodes a transcription repressor which associates with SMRT and mSin3A. Biochem Biophys Res Commun. 1999;264(3):871–877. PubMed PMID: 10544023.
  • Wang LC, Kuo F, Fujiwara Y, et al. Yolk sac angiogenic defect and intra‐embryonic apoptosis in mice lacking the Ets‐related factor TEL. Embo J. 1997;16(14):4374–4383. PubMed PMID: 9250681.
  • Wang LC, Swat W, Fujiwara Y, et al. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes Dev. 1998;12(15):2392–2402. PubMed PMID: 9694803.
  • Hock H, Meade E, Medeiros S, et al. Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev. 2004;18(19):2336–2341. PubMed PMID: 15371326.
  • Moriyama T, Metzger ML, Wu G, et al. Germline genetic variation in ETV6 and risk of childhood acute lymphoblastic leukaemia: a systematic genetic study. Lancet Oncol. 2015;16(16):1659–1666. PubMed PMID: 26522332.
  • Melazzini F, Palombo F, Balduini A, et al. Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia. Haematologica. 2016 Nov;101(11):1333–1342. PubMed PMID: 27365488; PubMed Central PMCID: PMC5394865.
  • Topka S, Vijai J, Walsh MF, et al. Germline ETV6 mutations confer susceptibility to acute lymphoblastic leukemia and thrombocytopenia. PLoS Genet. 2015;11(6):e1005262. PubMed PMID: 26102509.
  • Noetzli L, Lo RW, Lee-Sherick AB, et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat Genet. 2015 May;47(5):535–538. PubMed PMID: 25807284; PubMed Central PMCID: PMC4631613.
  • Zhang MY, Churpek JE, Keel SB, et al. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet. 2015 Feb;47(2):180–185. PubMed PMID: 25581430; PubMed Central PMCID: PMC4540357.
  • Di Paola J, Porter CC. ETV6-related thrombocytopenia and leukemia predisposition. Blood. 2019 Aug 22;134(8):663–667. PubMed PMID: 31248877.
  • Rampersaud E, Ziegler DS, Iacobucci I, et al. Germline deletion of ETV6 in familial acute lymphoblastic leukemia. Blood Adv. 2019 Apr 9;3(7):1039–1046. PubMed PMID: 30940639; PubMed Central PMCID: PMC6457220.
  • Junk SV, Klein N, Schreek S, et al. TP53, ETV6 and RUNX1 germline variants in a case series of patients developing secondary neoplasms after treatment for childhood acute lymphoblastic leukemia. Haematologica. 2019;104(9):e402. PubMed PMID: 31289210.
  • Wang M, Gu D, Du M, et al. Common genetic variation in ETV6 is associated with colorectal cancer susceptibility. Nat Commun. 2016 May;5(7):11478. PubMed PMID: 27145994; PubMed Central PMCID: PMC4858728.
  • Poggi M, Canault M, Favier M, et al. Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors. Haematologica. 2017;102(2):282–294. PubMed PMID: 27663637.
  • Merkenschlager M. Ikaros in immune receptor signaling, lymphocyte differentiation, and function. FEBS Lett. 2010 Dec 15;584(24):4910–4914. PubMed PMID: 20888815.
  • Georgopoulos K. The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma. Genes Dev. 2017 Mar 1;31(5):439–450. PubMed PMID: 28385788; PubMed Central PMCID: PMC5393059.
  • Olsson L, Johansson B. Ikaros and leukaemia. Br J Haematol. 2015;169(4):479–491. PubMed PMID: 25753742.
  • Nutt SL, Kee BL. The transcriptional regulation of B cell lineage commitment. Immunity. 2007;26(6):715–725. PubMed PMID: 17582344.
  • Mullighan CG, Phillips LA, Su X, et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science. 2008 Nov 28;322(5906):1377–1380. PubMed PMID: 19039135; PubMed Central PMCID: PMC2746051.
  • Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009 Jan 29;360(5):470–480. PubMed PMID: 19129520; PubMed Central PMCID: PMC2674612.
  • Churchman ML, Qian M, Te Kronnie G, et al. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. Cancer Cell. 2018 May 14;33(5):937–948.e938. PubMed PMID: 29681510; PubMed Central PMCID: PMC5953820.
  • Boutboul D, Kuehn HS, Van de Wyngaert Z, et al. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. J Clin Invest. 2018 Jul 2;128(7):3071–3087. PubMed PMID: 29889099; PubMed Central PMCID: PMC6026000.
  • Kuehn HS, Boisson B, Cunningham-Rundles C, et al. Loss of B cells in patients with heterozygous mutations in IKAROS. N Engl J Med. 2016 Mar 17;374(11):1032–1043. PubMed PMID: 26981933; PubMed Central PMCID: PMC4836293.
  • Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746–759. PubMed PMID: 20876176.
  • Tartaglia M, Mehler EL, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001 Dec;29(4):465–468. PubMed PMID: 11704759.
  • Cave H, Caye A, Strullu M, et al. Acute lymphoblastic leukemia in the context of RASopathies. Eur J Med Genet. 2016 Mar;59(3):173–178. PubMed PMID: 26855057.
  • Singer ST, Hurst D, Addiego JE Jr. Bleeding disorders in Noonan syndrome: three case reports and review of the literature. J Pediatr Hematol Oncol. 1997 Mar-Apr;19(2):130–134. PubMed PMID: 9149742.
  • Jongmans MC, van der Burgt I, Hoogerbrugge PM, et al. Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet. 2011 Aug;19(8):870–874. PubMed PMID: 21407260; PubMed Central PMCID: PMC3172922.
  • Kratz CP, Franke L, Peters H, et al. Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes. Br J Cancer. 2015 Apr 14;112(8):1392–1397. PubMed PMID: 25742478; PubMed Central PMCID: PMC4402457.
  • Neel BG, Gu H, Pao L. The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 2003;28(6):284–293. PubMed PMID: 12826400.
  • Tartaglia M, Niemeyer CM, Fragale A, et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet. 2003 Jun;34(2):148–150. PubMed PMID: 12717436.
  • Emanuel PD, Bates LJ, Castleberry RP, et al. Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood. 1991;77(5):925–929. PubMed PMID: 1704804.
  • Pandey R, Saxena M, Kapur R. Role of SHP2 in hematopoiesis and leukemogenesis. Curr Opin Hematol. 2017 Jul;24(4):307–313. PubMed PMID: 28306669; PubMed Central PMCID: PMC5709049.
  • Chan G, Cheung LS, Yang W, et al. Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells. Blood. 2011 Apr 21;117(16):4253–4261. PubMed PMID: 21398220; PubMed Central PMCID: PMC3087477.
  • Zhu HH, Ji K, Alderson N, et al. Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool. Blood. 2011 May 19;117(20):5350–5361. PubMed PMID: 21450902; PubMed Central PMCID: PMC3109710.
  • Dong L, Yu W-M, Zheng H, et al. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature. 2016;539(7628):304. PubMed PMID: 27783593.
  • Xu D, Wang S, Yu W-M, et al. A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells. Blood. 2010;116(18):3611–3621. PubMed: PMID: 20651068.
  • Jerchel IS, Hoogkamer AQ, Aries IM, et al. RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia. Leukemia. 2018 Apr;32(4):931–940. PubMed PMID: 28972594; PubMed Central PMCID: PMC5886052.
  • Riccardi VM. The prenatal diagnosis of NF-1 and NF-2. J Dermatol. 1992 Nov;19(11):885–891. PubMed PMID: 1293178.
  • Wimmer K, Rosenbaum T, Messiaen L. Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1. Clin Genet. 2017 Apr;91(4):507–519. PubMed PMID: 27779754.
  • Shannon KM, O’Connell P, Martin GA, et al. Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N Engl J Med. 1994 Mar 3;330(9):597–601. PubMed PMID: 8302341.
  • Le DT, Kong N, Zhu Y, et al. Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood. 2004 Jun 1;103(11):4243–4250. PubMed PMID: 14982883.
  • McClatchey AI. Neurofibromatosis. Annu Rev Pathol. 2007;2:191–216. PubMed PMID: 18039098.
  • Friedman J. Neurofibromatosis 1, GeneReviews. Seattle: Copyright University of Washington; 2013. 1997. PubMed PMID: 20301288.
  • Balgobind BV, Van Vlierberghe P, van den Ouweland AM, et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. Blood. 2008 Apr 15;111(8):4322–4328. PubMed PMID: 18172006.
  • Philpott C, Tovell H, Frayling IM, et al. The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics. 2017 Jun 21;11(1):13. PubMed PMID: 28637487; PubMed Central PMCID: PMC5480124.
  • Bader JL, Miller RW. Neurofibromatosis and childhood leukemia. J Pediatr. 1978 Jun;92(6):925–929. PubMed PMID: 96239.
  • Stiller CA, Chessells JM, Fitchett M. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br J Cancer. 1994 Nov;70(5):969–972. PubMed PMID: 7947106; PubMed Central PMCID: PMC2033537.
  • Mullighan CG. The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174–180. PubMed PMID: 25696852.
  • Liu Y, Easton J, Shao Y, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017 Aug;49(8):1211–1218. PubMed PMID: 28671688; PubMed Central PMCID: PMC5535770.
  • Holmfeldt L, Wei L, Diaz-Flores E, et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 2013 Mar;45(3):242–252. PubMed PMID: 23334668; PubMed Central PMCID: PMC3919793.
  • Zhang YY, Vik TA, Ryder JW, et al. Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. J Exp Med. 1998 Jun 1;187(11):1893–1902. PubMed PMID: 9607929; PubMed Central PMCID: PMC2212307.
  • Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood. 2017 Apr 13;129(15):2070–2082. PubMed PMID: 28179279; PubMed Central PMCID: PMC5391618.
  • Schlegelberger B, Heller PG. RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM). Semin Hematol. 2017 Apr;54(2):75–80. PubMed PMID: 28637620.
  • De Braekeleer E, Douet-Guilbert N, Morel F, et al. RUNX1 translocations and fusion genes in malignant hemopathies. Future Oncol. 2011 Jan;7(1):77–91. PubMed PMID: 21174539.
  • Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012 Jan 11;481(7380):157–163. PubMed PMID: 22237106; PubMed Central PMCID: PMC3267575.
  • Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999 Oct;23(2):166–175. PubMed PMID: 10508512.
  • Kanagal-Shamanna R, Loghavi S, DiNardo CD, et al. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation. Haematologica. 2017 Oct;102(10):1661–1670. PubMed PMID: 28659335; PubMed Central PMCID: PMC5622850.
  • Preudhomme C, Renneville A, Bourdon V, et al. High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder. Blood. 2009 May 28;113(22):5583–5587. PubMed PMID: 19357396.
  • Latger-Cannard V, Philippe C, Bouquet A, et al. Haematological spectrum and genotype-phenotype correlations in nine unrelated families with RUNX1 mutations from the French network on inherited platelet disorders. Orphanet J Rare Dis. 2016 Apr 26;11:49. PubMed PMID: 27112265; PubMed Central PMCID: PMC4845427.
  • Michaud J, Wu F, Osato M, et al. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood. 2002 Feb 15;99(4):1364–1372. PubMed PMID: 11830488.
  • Nishimoto N, Imai Y, Ueda K, et al. T cell acute lymphoblastic leukemia arising from familial platelet disorder. Int J Hematol. 2010 Jul;92(1):194–197. PubMed PMID: 20549580.
  • Bluteau D, Gilles L, Hilpert M, et al. Down-regulation of the RUNX1-target gene NR4A3 contributes to hematopoiesis deregulation in familial platelet disorder/acute myelogenous leukemia. Blood. 2011 Dec 8;118(24):6310–6320. PubMed PMID: 21725049.
  • Antony-Debre I, Duployez N, Bucci M, et al. Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia. Leukemia. 2016;30:999–1002. PubMed PMID: 26316320.
  • Prebet T, Carbuccia N, Raslova H, et al. Concomitant germ-line RUNX1 and acquired ASXL1 mutations in a T-cell acute lymphoblastic leukemia. Eur J Haematol. 2013 Sep;91(3):277–279. PubMed PMID: 23692290.
  • 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(8):3444–3449. PubMed PMID: 8622955.
  • Okuda T, Van Deursen J, Hiebert SW, et al. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996;84(2):321–330. PubMed PMID: 8565077.
  • Sasaki K, Yagi H, Bronson RT, 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(22):12359–12363. PubMed PMID: 8901586.
  • Growney JD, Shigematsu H, Li Z, et al. Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood. 2005;106(2):494–504. PubMed PMID: 15784726.
  • Bellissimo DC, Speck NA. RUNX1 mutations in inherited and sporadic leukemia. Front Cell Dev Biol. 2017;5:111. PubMed PMID: 29326930.
  • Lane DP. Cancer. p53, guardian of the genome. Nature. 1992;358:15–16. PubMed PMID: 1614522.
  • Pinto EM, Ribeiro RC, Figueiredo BC, et al. TP53-associated pediatric malignancies. Genes Cancer. 2011 Apr;2(4):485–490. PubMed PMID: 21779516; PubMed Central PMCID: PMC3135643.
  • Weisz L, Oren M, Rotter V. Transcription regulation by mutant p53. Oncogene. 2007 Apr 2;26(15):2202–2211. PubMed PMID: 17401429.
  • Lane D. p53 and human cancers. Br Med Bull. 1994;50(3):582–599. PubMed PMID: 7987642.
  • Correa H. Li-Fraumeni syndrome. J Pediatr Genet. 2016 Jun;5(2):84–88. PubMed PMID: 27617148; PubMed Central PMCID: PMC4918696.
  • Mai PL, Best AF, Peters JA, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the national cancer institute Li-Fraumeni syndrome cohort. Cancer. 2016 Dec 1;122(23):3673–3681. PubMed PMID: 27496084; PubMed Central PMCID: PMC5115949.
  • Gonzalez KD, Noltner KA, Buzin CH, et al. Beyond Li Fraumeni syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol. 2009;27(8):1250–1256. PubMed PMID: 19204208.
  • Ruijs MW, Verhoef S, Rookus MA, et al. TP53 germline mutation testing in 180 families suspected of Li–Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010;47(6):421–428. PubMed PMID: 20522432.
  • Bougeard G, Renaux-Petel M, Flaman JM, et al. Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol. 2015 Jul 20;33(21):2345–2352. PubMed PMID: 26014290.
  • Nichols KE, Malkin D, Garber JE, et al. Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev. 2001 Feb;10(2):83–87. PubMed PMID: 11219776.
  • Qian M, Cao X, Devidas M, et al. TP53 germline variations influence the predisposition and prognosis of B-cell acute lymphoblastic leukemia in children. J Clin Oncol. 2018 Feb 20;36(6):591–599. PubMed PMID: 29300620; PubMed Central PMCID: PMC5815403.
  • Zhang J, Walsh MF, Wu G, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med. 2015;373(24):2336–2346. PubMed PMID: 26580448.
  • Churpek JE, Marquez R, Neistadt B, et al. Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia. Cancer. 2016 Jan 15;122(2):304–311. PubMed PMID: 26641009; PubMed Central PMCID: PMC4707981.
  • Wimmer K, Etzler J. Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? Hum Genet. 2008;124(2):105–122. PubMed PMID: 18709565.
  • Quinn E, Nichols KE. Cancer predisposition syndromes associated with myeloid malignancy. Semin Hematol. 2017 Apr;54(2):115–122. PubMed PMID: 28637615.
  • Miyashita K, Fujii K, Taguchi K, et al. A specific mode of microsatellite instability is a crucial biomarker in adult T-cell leukaemia/lymphoma patients. J Cancer Res Clin Oncol. 2017 Mar;143(3):399–408. PubMed PMID: 27783137; PubMed Central PMCID: PMC5306345.
  • Kohlmann W, Gruber S. Lynch syndrome, GeneReviews. Seattle: Copyright University of Washington; 1993. PubMed PMID: 20301390.
  • Tabori U, Hansford JR, Achatz MI, et al. Clinical management and tumor surveillance recommendations of inherited mismatch repair deficiency in childhood. Clin Cancer Res. 2017 Jun 1;23(11):e32–e37. PubMed PMID: 28572265.
  • Lavoine N, Colas C, Muleris M, et al. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort. J Med Genet. 2015 Nov;52(11):770–778. PubMed PMID: 26318770.
  • Vasen HF, Ghorbanoghli Z, Bourdeaut F, et al. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European consortium “Care for CMMR-D” (C4CMMR-D). J Med Genet. 2014 May;51(5):283–293. PubMed PMID: 24556086.
  • Ripperger T, Schlegelberger B. Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome. Eur J Med Genet. 2016 Mar;59(3):133–142. PubMed PMID: 26743104.
  • Wimmer K, Kratz CP, Vasen HF, et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘care for CMMRD’ (C4CMMRD). J Med Genet. 2014 Jun;51(6):355–365. PubMed PMID: 24737826.
  • Lage H, Dietel M. Involvement of the DNA mismatch repair system in antineoplastic drug resistance. J Cancer Res Clin Oncol. 1999;125(3–4):156–165. PubMed PMID: 10235469.
  • Shinsato Y, Furukawa T, Yunoue S, et al. Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma. Oncotarget. 2013 Dec;4(12):2261–2270. PubMed PMID: 24259277; PubMed Central PMCID: PMC3926825.
  • Stritzelberger J, Distel L, Buslei R, et al. Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine. Clin Transl Oncol. 2018 Apr;20(4):508–516. PubMed PMID: 28825189.
  • Fink D, Aebi S, Howell SB. The role of DNA mismatch repair in drug resistance. Clin Cancer Res. 1998 Jan;4(1):1–6. PubMed PMID: 9516945.
  • Bardelli A, Cahill DP, Lederer G, et al. Carcinogen-specific induction of genetic instability. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5770–5775. PubMed PMID: 11296254; PubMed Central PMCID: PMC33288.
  • Campbell BB, Light N, Fabrizio D, et al. Comprehensive analysis of hypermutation in human cancer. Cell. 2017 Nov 16;171(5):1042–1056. PubMed PMID: 29056344; PubMed Central PMCID: PMC5849393.
  • Westdorp H, Kolders S, Hoogerbrugge N, et al. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome. Cancer Lett. 2017 Sep;10(403):159–164. PubMed PMID: 28645564.
  • Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509–2520. PubMed PMID: 26028255; PubMed Central PMCID: PMC4481136.
  • Bouffet E, Larouche V, Campbell BB, et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol. 2016 Jul 1;34(19):2206–2211. PubMed PMID: 27001570.
  • AlHarbi M, Ali Mobark N, AlMubarak L, et al. Durable response to nivolumab in a pediatric patient with refractory glioblastoma and constitutional biallelic mismatch repair deficiency. Oncologist. 2018 Dec;23(12):1401–1406. PubMed PMID: 30104292; PubMed Central PMCID: PMC6292541.
  • Pavelka Z, Zitterbart K, Noskova H, et al. Effective immunotherapy of glioblastoma in an adolescent with constitutional mismatch repair-deficiency syndrome. Klin Onkol. 2019;32(1):70–74. PubMed PMID: 30764633.
  • Fong C-T, Brodeur GM. Down’s syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genet Cytogenet. 1987;28(1):55–76. PubMed PMID: 2955886.
  • Brewster H, Cannon H Acute lymphatic leukemia: report of case in eleventh month mongolian idiot. New Orleans Med Surg J. 1930;82:872–873.
  • Stoll C, Dott B, Alembik Y, et al. Associated congenital anomalies among cases with Down syndrome. Eur J Med Genet. 2015;58(12):674–680. PubMed PMID: 26578241.
  • Mateos MK, Barbaric D, Byatt S-A, et al. Down syndrome and leukemia: insights into leukemogenesis and translational targets. Transl Pediatr. 2015;4(2):76. PubMed PMID: 26835364.
  • Li Y, Schwab C, Ryan SL, et al. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature. 2014;508(7494):98. PubMed PMID: 24670643.
  • Buitenkamp TD, Izraeli S, Zimmermann M, et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014;123(1):70–77. PubMed PMID: 24222333.
  • Roberts I, Izraeli S. Haematopoietic development and leukaemia in Down syndrome. Br J Haematol. 2014;167(5):587–599. PubMed PMID: 25155832.
  • Athale UH, Puligandla M, Stevenson KE, et al. Outcome of children and adolescents with Down syndrome treated on Dana‐Farber cancer institute acute lymphoblastic leukemia consortium protocols 00–001 and 05-001. Pediatr Blood Cancer. 2018;65(10):e27256. PubMed PMID: 29878490.
  • Matloub Y, Rabin KR, Ji L, et al. Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children’s Oncology Group. Blood Adv. 2019;3(11):1647–1656. PubMed PMID: 31160295.
  • Forestier E, Izraeli S, Beverloo B, et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood. 2008;111(3):1575–1583. PubMed PMID: 17971484.
  • Mullighan CG, Collins-Underwood JR, Phillips LA, et al. Rearrangement of CRLF2 in B-progenitor–and Down syndrome–associated acute lymphoblastic leukemia. Nat Genet. 2009;41(11):1243. PubMed PMID: 19838194.
  • Hertzberg L, Vendramini E, Ganmore I, et al. Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the international BFM study group. Blood. 2010;115(5):1006–1017. PubMed PMID: 19965641.
  • Bercovich D, Ganmore I, Scott LM, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down’s syndrome. Lancet. 2008;372(9648):1484–1492. PubMed PMID: 18805579.
  • Kubota Y, Uryu K, Ito T, et al. Integrated genetic and epigenetic analysis revealed heterogeneity of acute lymphoblastic leukemia in Down syndrome. Cancer Sci. 2019;110(10):3358. PubMed PMID: 31385395.
  • Papaemmanuil E, Hosking FJ, Vijayakrishnan J, et al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet. 2009;41(9):1006–1010. PubMed PMID: 19684604.
  • Treviño LR, Yang W, French D, et al. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet. 2009;41(9):1001–1005. PubMed PMID: 19684603.
  • Migliorini G, Fiege B, Hosking FJ, et al. Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype. Blood. 2013;122(19):3298–3307. PubMed PMID: 23996088.
  • Perez-Andreu V, Roberts KG, Harvey RC, et al. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat Genet. 2013;45(12):1494. PubMed PMID: 24141364.
  • Ramsey LB, Bruun GH, Yang W, et al. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res. 2012;22(1):1–8. PubMed PMID: 22147369.
  • Qian M, Xu H, Perez-Andreu V, et al. Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics. Blood. 2019;133(7):724–729. PubMed PMID: 30510082.
  • Xu H, Yang W, Perez-Andreu V, et al. Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J Natl Cancer Inst. 2013;105(10):733–742. PubMed PMID: 23512250.
  • Brown AL, de Smith AJ, Gant VU, et al. Inherited genetic susceptibility of acute lymphoblastic leukemia in Down syndrome. Blood. 2019. doi: 10.1182/blood.2018890764. PubMed PMID: 31350265.
  • Vijayakrishnan J, Studd J, Broderick P, et al. Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia. Nat Commun. 2018;9(1):1340. PubMed PMID: 29632299.
  • Ellinghaus E, Stanulla M, Richter G, et al. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia. 2012;26(5):902. PubMed: PMID 22076464.
  • Xu H, Zhang H, Yang W, et al. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. Nature Comm. 2015;6:7553. doi: 10.1038/ncomms8553.
  • Sherborne AL, Hosking FJ, Prasad RB, et al. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet. 2010;42(6):492. PubMed PMID: 20453839.
  • Wiemels JL, Walsh KM, de Smith AJ, et al. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nat Commun. 2018;9(1):286. PubMed PMID: 29348612.
  • Hungate EA, Vora SR, Gamazon ER, et al. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology. Nat Commun. 2016;7:10635. PubMed PMID: 26868379.
  • Vijayakrishnan J, Kumar R, Henrion MY, et al. A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1. Leukemia. 2017;31(3):573. PubMed PMID: 27694927.
  • Qian M, Zhao X, Devidas M, et al. Genome-wide association study of susceptibility loci for T-cell acute lymphoblastic leukemia in children. J Natl Cancer Inst. 2019 Apr 2. PubMed PMID: 30938820. DOI:10.1093/jnci/djz043.
  • Kinlen L. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain. Lancet. 1988 Dec 10;2(8624):1323–1327. PubMed PMID: 2904050.
  • Greaves MF. Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia. 1988 Feb;2(2):120–125. PubMed PMID: 3278171.
  • Marcotte EL, Ritz B, Cockburn M, et al. Exposure to infections and risk of leukemia in young children. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1195–1203. PubMed PMID: 24793957.
  • Martin-Lorenzo A, Hauer J, Vicente-Duenas C, et al. Infection exposure is a causal factor in B-cell precursor acute lymphoblastic leukemia as a result of Pax5-inherited susceptibility. Cancer Discov. 2015 Dec;5(12):1328–1343. PubMed PMID: 26408659.
  • Ford AM, Palmi C, Bueno C, et al. The TEL-AML1 leukemia fusion gene dysregulates the TGF-β pathway in early B lineage progenitor cells. J Clin Invest. 2009;119(4):826–836. PubMed PMID: 19287094.
  • Mori H, Colman SM, Xiao Z, et al. Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci U S A. 2002;99(12):8242–8247. PubMed PMID: 12048236.
  • Drazer MW, Kadri S, Sukhanova M, et al. Prognostic tumor sequencing panels frequently identify germ line variants associated with hereditary hematopoietic malignancies. Blood Adv. 2018;2(2):146–150. PubMed PMID: 29365323.
  • Genovese G, Kahler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014 Dec 25;371(26):2477–2487. PubMed PMID: 25426838; PubMed Central PMCID: PMC4290021.
  • Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014 Dec 25;371(26):2488–2498. PubMed PMID: 25426837; PubMed Central PMCID: PMC4306669.
  • Desai AV, Perpich M, Godley LA. Clinical assessment and diagnosis of germline predisposition to hematopoietic malignancies: the University of Chicago experience. Front Pediatr. 2017;5:252. PubMed PMID: 29270394; PubMed Central PMCID: PMC5723667.
  • Chaudhary G, Dogra T, Raina A. Evaluation of blood, buccal swabs, and hair follicles for DNA profiling technique using STR markers. Croat Med J. 2015;56(3):239–245. PubMed PMID: 26088848.
  • Škerl P, Krajc M, Blatnik A, et al. Genetic testing and counseling of a recipient after bone marrow transplant from a sibling harboring a germline BRCA1 pathogenic mutation. Oncol Rep. 2017;38(1):279–282. PubMed PMID: 28586023.
  • Porter CC, Druley TE, Erez A, et al. Recommendations for surveillance for children with leukemia-predisposing conditions. Clin Cancer Res. 2017 Jun 1;23(11):e14–e22. PubMed PMID: 28572263.
  • McReynolds LJ, Savage SA. Pediatric leukemia susceptibility disorders: manifestations and management. Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):242–250. PubMed PMID: 29222262; PubMed Central PMCID: PMC6142612 interests.
  • Toledano SR, Lange BJ. Ataxia-telangiectasia and acute lymphoblastic leukemia. Cancer. 1980;45(7):1675–1678. PubMed PMID: 6929216.
  • Sandoval C, Swift M. Treatment of lymphoid malignancies in patients with ataxia‐telangiectasia. Med Pediatr Oncol. 1998;31(6):491–497. PubMed PMID: 9835901.
  • Schulz E, Valentin A, Ulz P, et al. Germline mutations in the DNA damage response genes BRCA1, BRCA2, BARD1 and TP53 in patients with therapy related myeloid neoplasms. J Med Genet. 2012 Jul;49(7):422–428. PubMed PMID: 22652532. PubMed PMID: 22652532.
  • Eyre J, Gardner-Medwin D, Summerfield G. Leukoencephalopathy after prophylactic radiation for leukaemia in ataxia telangiectasia. Arch Dis Child. 1988;63(9):1079–1080. PubMed PMID: 3178268.
  • Yanofsky RA, Seshia SS, Dawson AJ, et al. Ataxia-telangiectasia: atypical presentation and toxicity of cancer treatment. Can J Neurosci Nurs. 2009;36(4):462–467. PubMed PMID: 19650357.
  • Hamilton KV, Maese L, Marron JM, et al. Stopping leukemia in its tracks: should preemptive hematopoietic stem-cell transplantation be offered to patients at increased genetic risk for acute myeloid leukemia? J Clin Oncol. 2019 Jun 6:Jco1900181. PubMed PMID: 31170028.
  • Wang Z, Wilson CL, Easton J, et al. Genetic risk for subsequent neoplasms among long-term survivors of childhood cancer. J Clin Oncol. 2018;36(20):2078–2087. PubMed PMID: 29847298.
  • Parsons DW, Roy A, Yang Y, et al. Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol. 2016;2(5):616–624. PubMed PMID: 26822237.
  • Mody RJ, Wu Y-M, Lonigro RJ, et al. Integrative clinical sequencing in the management of refractory or relapsed cancer in youth. JAMA. 2015;314(9):913–925. PubMed PMID: 26325560.
  • Parekh C, Crooks GM. Critical differences in hematopoiesis and lymphoid development between humans and mice. J Clin Immunol. 2013;33(4):711–715. PubMed PMID: 23274800.
  • Jung M, Cordes S, Zou J, et al. GATA2 deficiency and human hematopoietic development modeled using induced pluripotent stem cells. Blood Adv. 2018;2(23):3553–3565. PubMed PMID: 30538114.
  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405. PubMed PMID: 27069254.

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