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The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome

Leukemia volume 30, pages 1816–1823 (2016)Cite this article

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Abstract

Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies.

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References

  1. Seewald L, Taub JW, Maloney KW, McCabe ER . Acute leukemias in children with Down syndrome. Mol Genet Metab 2012; 107: 25–30.

    Article  CAS  Google Scholar 

  2. Ross JA, Spector LG, Robison LL, Olshan AF . Epidemiology of leukemia in children with Down syndrome. Pediatr Blood Cancer 2005; 44: 8–12.

    Article  Google Scholar 

  3. Vis JC, Duffels MG, Winter MM, Weijerman ME, Cobben JM, Huisman SA et al. Down syndrome: a cardiovascular perspective. J Intellect Disabil Res 2009; 53: 419–425.

    Article  CAS  Google Scholar 

  4. Watt T, Robertson K, Jacobs RJ . Refractive error, binocular vision and accommodation of children with Down syndrome. Clin Exp Optom 2015; 98: 3–11.

    Article  Google Scholar 

  5. Ferreira-Vasques AT, Lamônica DA . Motor, linguistic, personal and social aspects of children with Down syndrome. J Appl Oral Sci 2015; 23: 424–430.

    Article  Google Scholar 

  6. Lange B . The management of neoplastic disorders of haematopoiesis in children with Down's syndrome. Br J Haematol 2000; 110: 512–524.

    Article  CAS  Google Scholar 

  7. Hasle H, Clemmensen IH, Mikkelsen M . Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet 2000; 355: 165–169.

    Article  CAS  Google Scholar 

  8. Yang Q, Rasmussen SA, Friedman JM . Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet 2002; 359: 1019–1025.

    Article  Google Scholar 

  9. Langebrake C, Creutzig U, Reinhardt D . Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts. Klin Padiatr 2005; 217: 126–134.

    Article  CAS  Google Scholar 

  10. Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down qsyndrome. Nat Genet 2002; 32: 148–152.

    Article  CAS  Google Scholar 

  11. Caldwell JT, Ge Y, Taub JW . Prognosis and management of acute myeloid leukemia in patients with Down syndrome. Expert Rev Hematol 2014; 7: 831–840.

    Article  CAS  Google Scholar 

  12. Creutzig U, van den Heuvel-Eibrink MM, Gibson B, Dworzak MN, Adachi S, de Bont E et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood 2012; 120: 3187–3205.

    Article  CAS  Google Scholar 

  13. Taga T, Watanabe T, Tomizawa D, Kudo K, Terui K, Moritake H et al. Preserved high probability of overall survival with significant reduction of chemotherapy for myeloid leukemia in Down syndrome: A Nationwide Prospective Study in Japan. Pediatr Blood Cancer 2016; 63: 248–254.

    Article  CAS  Google Scholar 

  14. Ge Y, Stout ML, Tatman DA, Jensen TL, Buck S, Thomas RL et al. GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia. J Natl Cancer Inst 2005; 97: 226–231.

    Article  CAS  Google Scholar 

  15. Maloney KW, Carroll WL, Carroll AJ, Devidas M, Borowitz MJ, Martin PL et al. Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children's Oncology Group. Blood 2010; 116: 1045–1050.

    Article  CAS  Google Scholar 

  16. Zeller B, Gustafsson G, Forestier E, Abrahamsson J, Clausen N, Heldrup J et al. Acute leukaemia in children with Down syndrome: a population-based Nordic study. Br J Haematol 2005; 128: 797–804.

    Article  Google Scholar 

  17. Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood 2014; 123: 70–77.

    Article  CAS  Google Scholar 

  18. Arico M, Ziino O, Valsecchi MG, Cazzaniga G, Baronci C, Messina C et al. Acute lymphoblastic leukemia and Down syndrome: presenting features and treatment outcome in the experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Cancer 2008; 113: 515–521.

    Article  Google Scholar 

  19. Zwaan CM, Kaspers GJ, Pieters R, Hahlen K, Janka-Schaub GE, van Zantwijk CH et al. Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood 2002; 99: 245–251.

    Article  CAS  Google Scholar 

  20. Bohnstedt C, Levinsen M, Rosthoj S, Zeller B, Taskinen M, Hafsteinsdottir S et al. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia. Leukemia 2013; 27: 866–870.

    Article  CAS  Google Scholar 

  21. Maloney KW, Wood B, Whitlock JA, Loh M, Raetz EA, Winick N et al. Event free (EFS) and overall survival (OS) for children with Down syndrome (DS) and B-lymhoblastic leukemia in Children's Oncology Group (COG) trials AALL0232 and AALL0331. Pediatr Blood Cancer 2014; 61: S4; abstract no. 4009.

    Google Scholar 

  22. Buitenkamp TD, Mathot RA, de Haas V, Pieters R, Zwaan CM . Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia. Haematologica 2010; 95: 1106–1113.

    Article  CAS  Google Scholar 

  23. Goto H, Kaneko T, Shioda Y, Kajiwara M, Sakashita K, Kitoh T et al. Hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and Down syndrome. Pediatr Blood Cancer 2015; 62: 148–152.

    Article  Google Scholar 

  24. Hitzler JK, He W, Doyle J, Cairo M, Camitta BM, Chan KW et al. Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome. Pediatr Blood Cancer 2014; 61: 1126–1128.

    Article  Google Scholar 

  25. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385: 517–528.

    Article  CAS  Google Scholar 

  26. Maude SL, Teachey DT, Porter DL, Grupp SA . CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 2015; 125: 4017–4023.

    Article  CAS  Google Scholar 

  27. Batlevi CL, Matsuki E, Brentjens RJ, Younes A . Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol 2016; 13: 25–40.

    Article  CAS  Google Scholar 

  28. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371: 1507–1517.

    Article  Google Scholar 

  29. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K et al. Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014; 6, 224ra25.

  30. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015; 16: 57–66.

    Article  CAS  Google Scholar 

  31. Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013; 121: 5154–5157.

    Article  CAS  Google Scholar 

  32. Annesley CE, Brown P . Novel agents for the treatment of childhood acute leukemia. Ther Adv Hematol 2015; 6: 61–79.

    Article  CAS  Google Scholar 

  33. Maude SL, Tasian SK, Vincent T, Hall JW, Sheen C, Roberts KG et al. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 2012; 120: 3510–3518.

    Article  CAS  Google Scholar 

  34. Tasian SK, Doral MY, Borowitz MJ, Wood BL, Chen IM, Harvey RC et al. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood 2012; 120: 833–842.

    Article  CAS  Google Scholar 

  35. Lane AA, Chapuy B, Lin CY, Tivey T, Li H, Townsend EC et al. Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nat Genet 2014; 46: 618–623.

    Article  CAS  Google Scholar 

  36. Thompson BJ, Bhansali R, Diebold L, Cook DE, Stolzenburg L, Casagrande AS et al. DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3. J Exp Med 2015; 212: 953–970.

    Article  CAS  Google Scholar 

  37. Olsson L, Johansson B . Ikaros and leukaemia. Br J Haematol 2015; 169: 479–491.

    Article  CAS  Google Scholar 

  38. Asai D, Imamura T, Suenobu S, Saito A, Hasegawa D, Deguchi T et al. IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan. Cancer Med 2013; 2: 412–419.

    Article  CAS  Google Scholar 

  39. Buitenkamp TD, Pieters R, Gallimore NE, van der Veer A, Meijerink JP, Beverloo HB et al. Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. Leukemia 2012; 26: 2204–2211.

    Article  CAS  Google Scholar 

  40. Kearney L, Gonzalez De Castro D, Yeung J, Procter J, Horsley SW, Eguchi-Ishimae M et al. Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood 2009; 113: 646–648.

    Article  CAS  Google Scholar 

  41. Tirado CA, Shabsovich D, Kim Y, Traum P, Pullarkat S, Kallen M et al. A case of B-cell acute lymphoblastic leukemia in a child with Down syndrome bearing a t(2;12)(p12;p13) involving ETV6 and biallelic IGH@ rearrangements. Biomarker Res 2015; 3: 11.

    Article  Google Scholar 

  42. Loudin MG, Wang J, Leung HC, Gurusiddappa S, Meyer J, Condos G et al. Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles. Leukemia 2011; 25: 1555–1563.

    Article  CAS  Google Scholar 

  43. Hertzberg L, Vendramini E, Ganmore I, Cazzaniga G, Schmitz M, Chalker J 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: 1006–1017.

    Article  CAS  Google Scholar 

  44. Izraeli S . Similar yet different. Blood 2010; 116: 1019–1020.

    Article  CAS  Google Scholar 

  45. Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet 2009; 41: 1243–1246.

    Article  CAS  Google Scholar 

  46. Russell LJ, Capasso M, Vater I, Akasaka T, Bernard OA, Calasanz MJ et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 2009; 114: 2688–2698.

    Article  CAS  Google Scholar 

  47. Yoda A, Yoda Y, Chiaretti S, Bar-Natan M, Mani K, Rodig SJ et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2010; 107: 252–257.

    Article  CAS  Google Scholar 

  48. Roll JD, Reuther GW . CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer Res 2010; 70: 7347–7352.

    Article  CAS  Google Scholar 

  49. Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 2014; 371: 1005–1015.

    Article  Google Scholar 

  50. Malinge S, Ben-Abdelali R, Settegrana C, Radford-Weiss I, Debre M, Beldjord K et al. Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood 2007; 109: 2202–2204.

    Article  CAS  Google Scholar 

  51. Bercovich D, Ganmore I, Scott LM, Wainreb G, Birger Y, Elimelech A et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet 2008; 372: 1484–1492.

    Article  CAS  Google Scholar 

  52. Gaikwad A, Rye CL, Devidas M, Heerema NA, Carroll AJ, Izraeli S et al. Prevalence and clinical correlates of JAK2 mutations in Down syndrome acute lymphoblastic leukaemia. Br J Haematol 2009; 144: 930–932.

    Article  CAS  Google Scholar 

  53. Rampal R, Levine RL . A primer on genomic and epigenomic alterations in the myeloproliferative neoplasms. Bailliere's Best Pract Clin Haematol 2014; 27: 83–93.

    Article  CAS  Google Scholar 

  54. Babon JJ, Lucet IS, Murphy JM, Nicola NA, Varghese LN . The molecular regulation of Janus kinase (JAK) activation. Biochem J 2014; 462: 1–13.

    Article  CAS  Google Scholar 

  55. Haan C, Behrmann I, Haan S . Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases. J Cell Mol Med 2010; 14: 504–527.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Shochat C, Tal N, Bandapalli OR, Palmi C, Ganmore I, te Kronnie G et al. Gain-of-function mutations in interleukin-7 receptor-alpha (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med 2011; 208: 901–908.

    Article  CAS  Google Scholar 

  57. Nikolaev SI, Garieri M, Santoni F, Falconnet E, Ribaux P, Guipponi M et al. Frequent cases of RAS-mutated Down syndrome acute lymphoblastic leukaemia lack JAK2 mutations. Nat Commun 2014; 5: 4654.

    Article  CAS  Google Scholar 

  58. Kirsammer G, Jilani S, Liu H, Davis E, Gurbuxani S, Le Beau MM et al. Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome. Blood 2008; 111: 767–775.

    Article  CAS  Google Scholar 

  59. Malinge S, Bliss-Moreau M, Kirsammer G, Diebold L, Chlon T, Gurbuxani S et al. Increased dosage of the murine chromosome 21 orthog Dyrk1a promotes megakaryoblastic leukemia in Down syndrome. J Clin Invest 2012; 122: 948–962.

    Article  CAS  Google Scholar 

  60. Hardy RR, Carmack CE, Shinton SA, Kemp JD, Hayakawa K . Resolution and characterization of pro-B and pre–pro-B cell stages in normal mouse bone marrow. J Exp Med 1991; 173: 1213–1225.

    Article  CAS  Google Scholar 

  61. Lim JH, West KL, Rubinstein Y, Bergel M, Postnikov YV, Bustin M . Chromosomal protein HMGN1 enhances the acetylation of lysine 14 in histone H3. EMBO J 2005; 24: 3038–3048.

    Article  CAS  Google Scholar 

  62. Roy A, Cowan G, Mead AJ, Filippi S, Bohn G, Chaidos A et al. Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21. Proc Natl Acad Sci USA 2012; 109: 17579–17584.

    Article  CAS  Google Scholar 

  63. Abbassi R, Johns TG, Kassiou M, Munoz L . DYRK1A in neurodegeneration and cancer: molecular basis and clinical implications. Pharmacol Ther 2015; 151: 87–98.

    Article  CAS  Google Scholar 

  64. Hammerle B, Ulin E, Guimera J, Becker W, Guillemot F, Tejedor FJ . Transient expression of Mnb/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling. Development 2011; 138: 2543–2554.

    Article  CAS  Google Scholar 

  65. Ding S, Shi J, Qian W, Iqbal K, Grundke-Iqbal I, Gong CX et al. Regulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A. Neurobiol Aging 2012; 33: 1389–1399.

    Article  CAS  Google Scholar 

  66. Barallobre MJ, Perier C, Bove J, Laguna A, Delabar JM, Vila M et al. DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease. Cell Death Dis 2014; 5: e1289.

    Article  CAS  Google Scholar 

  67. Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ et al. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 2009; 459: 1126–1130.

    Article  CAS  Google Scholar 

  68. Litovchick L, Florens LA, Swanson SK, Washburn MP, DeCaprio JA . DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly. Genes Dev 2011; 25: 801–813.

    Article  CAS  Google Scholar 

  69. Soppa U, Schumacher J, Florencio Ortiz V, Pasqualon T, Tejedor FJ, Becker W . The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle 2014; 13: 2084–2100.

    Article  CAS  Google Scholar 

  70. Chen JY, Lin JR, Tsai FC, Meyer T . Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the decision to enter the cell cycle. Mol Cell 2013; 52: 87–100.

    Article  CAS  Google Scholar 

  71. Mullighan CG . The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology 2014; 2014: 174–180.

    Article  Google Scholar 

  72. Moorman AV, Richards SM, Robinson HM, Strefford JC, Gibson BE, Kinsey SE et al. Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). Blood 2007; 109: 2327–2330.

    Article  CAS  Google Scholar 

  73. Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P et al. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014; 508: 98–102.

    Article  CAS  Google Scholar 

  74. Rand V, Parker H, Russell LJ, Schwab C, Ensor H, Irving J et al. Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia. Blood 2011; 117: 6848–6855.

    Article  CAS  Google Scholar 

  75. Patrick K, Wade R, Goulden N, Rowntree C, Hough R, Moorman AV et al. Outcome of Down syndrome associated acute lymphoblastic leukaemia treated on a contemporary protocol. Br J Haematol 2014; 165: 552–555.

    Article  Google Scholar 

  76. Lundin C, Forestier E, Klarskov Andersen M, Autio K, Barbany G, Cavelier L et al. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries. J Hematol Oncol 2014; 7: 32.

    Article  Google Scholar 

  77. Whitlock JA, Sather HN, Gaynon P, Robison LL, Wells RJ, Trigg M et al. Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children's Cancer Group study. Blood 2005; 106: 4043–4049.

    Article  CAS  Google Scholar 

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Acknowledgements

This review was supported by grants from the National Institutes of Health (R01 CA101774, to JC), the Rally and Bear Necessities Foundations (to JC), the Unites States–Israel Binational Science Foundation (to SI and JC), the Samuel Waxman Cancer Research Foundation (to SI and JC), the Israel Science Foundation Legacy Program (to SI), the Israel Cancer Research Foundation (to SI) and Children with Cancer UK (to SI). This review is also supported, in part, by an Alpha Omega Alpha Carolyn L Kuckein Student Research Fellowship.

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  1. P Lee and R Bhansali: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology/Oncology/Stem Cell Transplant, Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    P Lee & N Hijiya

  2. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    R Bhansali & J D Crispino

  3. Edmond and Lily Safra, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel

    S Izraeli

  4. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    N Hijiya

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Correspondence to N Hijiya or J D Crispino.

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Dr Hijiya is a consultant for Novartis. The other authors declare no conflict of interest.

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Lee, P., Bhansali, R., Izraeli, S. et al. The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome. Leukemia 30, 1816–1823 (2016). https://doi.org/10.1038/leu.2016.164

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