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Вопросы гематологии/онкологии и иммунопатологии в педиатрии

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Гемопоэз и лейкозы у пациентов с синдромом Дауна

https://doi.org/10.24287/1726-1708-2015-14-3-13-33

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Аннотация

Дети с трисомией 21-й хромосомы (синдром Дауна - СД) имеют высокий риск развития как миелоидных, так и В-клеточного лимфобластного лейкозов. Миелоидным лейкозам часто предшествует транзиторный неонатальный предлейкемический синдром - транзиторный аномальный миелопоэз (ТАМ). Последний является результатом одно- временного наличия трисомии 21-й хромосомы и приобретенных соматических «усекающих» N-терминальный конец белка мутаций ключевого гемопоэтического транскрипционного фактора - гена GATA1 . Эти мутации, которые не являются лейкемогенными при отсутствии трисомии 21-й хромосомы, обнаруживаются у ⅓ новорожденных с СД. Анализ гемопоэтических клеток печени плода и эмбриональных стволовых клеток человека показывает, что трисомия 21-й хромосомы сама по себе существенно меняет гемопоэз плода. Следовательно, у детей с СД наблюдаются много- численные дефекты гемопоэза даже при отсутствии ТАМ. Хотя исследования на моделях мышей показали роль нере- гулируемой экспрессии некоторых генов, расположенных на 21-й хромосоме, в развитии лейкоза, участие этих генов в лейкемогенезе человека остается неизученным. Поскольку трисомия 21-й хромосомы обнаруживается во всех эмбриональных клетках, в основе патогенеза лейкозов, ассоциированных с СД, лежит комплексное взаимодействие между нерегулируемой экспрессией генов в гемопоэтических клетках и их микроокружением у плода.

Об авторах

I. Roberts
University of Oxford
Россия


S. Izraeli
Sheba Medical Centre; Sackler School of Medicine
Россия


Список литературы

1. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet. 2000;355(9199):165-9

2. Zipursky A. Susceptibility to leukemia and resistance to solid tumors in Down syndrome. Pediatr Res. 2000;47(6):704

3. Malinge S, Izraeli S, Crispino JD. Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood. 2009;113(12): 2619-28

4. Roy A, Roberts I, Norton A, Vyas P. Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. Br J Haematol. 2009;147(1):3-12

5. Izraeli S, Vora A, Zwaan CM, Whitlock J. How I treat ALL in Down's syndrome: pathobiology and management. Blood. 2014;123(1):35-40

6. Zwaan MC, Reinhardt D, Hitzler J, Vyas P. Acute leukemias in children with Down syndrome. Pediatr Clin North Am. 2008;55(1):53-70

7. Taga T, Saito AM, Kudo K, Tomizawa D, Terui K, Moritake H, et al. Clinical characteristics and outcome of refractory/relapsed myeloid leukemia in children with Down syndrome. Blood. 2012;120(9):1810-5

8. O'Brien MM, Cao X, Pounds S, Dahl GV, Raimondi SC, Lacayo NJ, et al. Prognostic features in acute megakaryoblastic leukemia in children without Down syndrome: a report from the AML02 multicenter trial and the Children's Oncology Group Study POG 9421. Leukemia. 2013;27(3):731-4

9. 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(1):70-7

10. Forestier E, Izraeli S, Beverloo B, Haas O, Pession A, Michalová K, et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood. 2008;111(3):1575-83

11. 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(9648):1484-92

12. 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(11):1243-6

13. 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(13):2688-98

14. 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(5):1006-17

15. Shochat C, Tal N, Bandapalli OR, Palmi C, Ganmore I, te Kronnie G, et al. Gain-of- function mutations in interleukin-7 receptor- (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med. 2011;208(5):901-8

16. Tal N, Shochat C, Geron I, Bercovich D, Izraeli S. Interleukin 7 and thymic stromal lymphopoietin: from immunity to leukemia. Cell Mol Life Sci. 2014;71(3):365-78

17. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277-82

18. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51

19. Langebrake C, Creutzig U, Reinhardt D. Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs signifi- cantly from other diseases with morphologically identical or similar blasts. Klin Pädiatr. 2005;217(3):126-34

20. Ge Y, Jensen TL, Stout ML, Flatley RM, Grohar PJ, Ravindranath Y, et al. The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines. Cancer Res. 2004;64(2):728-35

21. 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(3):226-31

22. Edwards H, Xie C, LaFiura KM, Dombkowski AA, Buck SA, Boerner JL, et al. RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia. Blood. 2009;114(13):2744-52

23. Nikolaev SI, Santoni F, Vannier A, Falconnet E, Giarin E, Basso G, et al. Exome sequencing identifies putative drivers of progression of transient myeloproliferative disorder to AMKL in infants with Down syndrome. Blood. 2013;122(4):554-61

24. Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45(11):1293-9

25. Greaves M. Pre-natal origins of childhood leukemia. Rev Clin Exp Hematol. 2003;7(3):233-45

26. Klusmann JH, Creutzig U, Zimmermann M, Dworzak M, Jorch N, Langebrake C, et al. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood. 2008;111(6):2991-8

27. Zipursky A. Transient leukaemia--a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol. 2003;120(6):930-8

28. Gamis AS, Alonzo TA, Gerbing RB, Hilden JM, Sorrell AD, Sharma M, et al. Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971. Blood. 2011;118(26):6752-9

29. Roberts I, Alford K, Hall G, Juban G, Richmond H, Norton A, et al. GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia. Blood. 2013;122(24): 3908-17

30. Groet J, McElwaine S, Spinelli M, Rinaldi A, Burtscher I, Mulligan C, et al. Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder. Lancet. 2003;361(9369):1617-20

31. Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood. 2003;101(11):4301-4

32. Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J, et al. Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. Blood. 2003;102(3):981-6

33. 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

34. Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C. Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome. Blood. 2007;110(6):2128-3

35. Heald B, Hilden JM, Zbuk K, Norton A, Vyas P, Theil KS, Eng C. Severe TMD/AMKL with GATA1 mutation in a stillborn fetus with Down syndrome. Nat Clin Pract Oncol. 2007;4(7):433-8

36. Massey GV, Zipursky A, Chang MN, Doyle JJ, Nasim S, Taub JW, et al. A pros- pective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481. Blood. 2006;107(12):4606-13

37. Maroz A, Stachorski L, Emmrich S, Reinhardt K, Xu J, Shao Z, et al. GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia. Leukemia. 2014;28(6):1259-70

38. Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, et al. Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood. 1998;91(2):608-15

39. Hasle H, Abrahamsson J, Arola M, Karow A, O'Marcaigh A, Reinhardt D, et al. Myeloid leukemia in children 4 years or older with Down syndrome often lacks GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic AML. Leukemia. 2008;22(7):1428-30

40. 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 syndrome. Nat Genet. 2002;32(1):148-52

41. Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T, et al. Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood. 2003;102(8):2960-8

42. Alford KA, Reinhardt K, Garnett C, Norton A, Böhmer K, von Neuhoff C, et al. Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia. Blood. 2011;118(8):2222-38

43. Taub JW, Mundschau G, Ge Y, Poulik JM, Qureshi F, Jensen T, et al. Prenatal origin of GATA1 mutations may be an initiating step in the development of megakaryocytic leukemia in Down syndrome. Blood. 2004;104(5):1588-9

44. Hollanda LM, Lima CS, Cunha AF, Albuquerque DM, Vassallo J, Ozelo MC, et al. An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Nat Genet. 2006;38(7):807-12

45. Ganmore I, Smooha G, Izraeli S. Constitutional aneuploidy and cancer predisposition. Hum Mol Genet. 2009;18(R1):R84-93

46. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, et al. Mutational processes molding the genomes of 21 breast cancers. Cell. 2012;149(5):179-93

47. Nižetić D, Groet J. Tumorigenesis in Down syndrome: big lessons from a small chromosome. Nat Rev Cancer. 2012;12(10):721-32

48. Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, et al. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet. 2000;24(3):266-70

49. Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio JA, Beggs AH, et al. Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest. 2012;122(7):2439-43

50. Klar J, Khalfallah A, Arzoo PS, Gazda HT, Dahl N. Recurrent GATA1 mutations in Diamond-Blackfan anaemia. Br J Haematol. 2014;166(6):949-51

51. Salek-Ardakani S, Smooha G, de Boer J, Sebire NJ, Morrow M, Rainis L, et al. ERG is a megakaryocytic oncogene. Cancer Res. 2009;69(11):4665-73

52. Toki T, Kanezaki R, Kobayashi E, Kaneko H, Suzuki M, Wang R, et al. Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome. Blood. 2013;121(16):3181-4

53. Klusmann JH, Godinho FJ, Heitmann K, Maroz A, Koch ML, Reinhardt D, et al. Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis. Genes Dev. 2010;24(15):1659-72

54. Li Z, Godinho FJ, Klusmann JH, Garriga-Canut M, Yu C, Orkin SH. Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1. Nat Genet. 2005;37(6):613-9

55. Chou ST, Opalinska JB, Yao Y, Fernandes MA, Kalota A, Brooks JS, et al. Trisomy 21 enhances human fetal erythro-megakaryocytic development. Blood. 2008;112(12):4503-6

56. Tunstall-Pedoe O, Roy A, Karadimitris A, de la Fuente J, Fisk NM, Bennett P, et al. Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood. 2008;112(12):4507-11

57. 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(43):17579-84

58. Chou ST, Byrska-Bishop M, Tober JM, Yao Y, Vandorn D, Opalinska JB, et al. Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells. Proc Natl Acad Sci USA. 2012; 109(43):17573-8

59. Izraeli S. Trisomy 21 tilts the balance. Blood. 2008;112(12):4361-2

60. MacLean GA, Menne TF, Guo G, Sanchez DJ, Park IH, Daley GQ, et al. Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic induced pluripotent cells. Proc Natl Acad Sci USA. 2012;109(43):17567-72

61. Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156(2):189-93

62. 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(13):4043-9

63. Zhang CC, Lodish HF. Insulin-like growth factor 2 expressed in a novel fetal liver population is a growth factor for hematopoietic stem cells. Blood. 2004;103(7):2513-21

64. Garrett RW, Emerson SG. The role of parathyroid hormone and insulin-like growth factors in hematopoietic niches: physiology and pharmacology. Mol Cell Endocrinol. 2006;288(1-2):6-10

65. Chou S, Lodish HF. Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells. Proc Natl Acad Sci USA. 2010;107(17):7799-804

66. Starc TJ. Erythrocyte macrocytosis in infants and children with Down syndrome. J Pediatr. 1992;121(4):578-81

67. Kivivuori SM, Rajantie J, Siimes MA. Peripheral blood cell counts in infants with Down's syndrome. Clin Genet. 1996;49(1):15-9

68. Henry E, Walker D, Wiedmeier SE, Christensen RD. Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system. Am J Med Genet A. 2007;143A(1):42-50

69. Douglas SD. Down syndrome: immunologic and epidemiologic associations- enigmas remain. J Pediatr. 2005;147(6):723-5

70. de Hingh YC, van der Vossen PW, Gemen EF, Mulder AB, Hop WC, Brus F, et al. Intrinsic abnormalities of lymphocyte counts in children with down syndrome. J Pediatr. 2005;147(6):744-7

71. Verstegen RH, Kusters MA, Gemen EF, De Vries E. Down syndrome B-lymphocyte subpopulations: intrinsic defect or decreased T-lymphocyte help. Pediatr Res. 2010;67(5):563-9

72. Roizen NJ, Amarose AP. Hematologic abnormalities in children with Down syndrome. Am J Med Genet. 1993;46(5):510-2

73. David O, Fiorucci GC, Tosi MT, Altare F, Valori A, Saracco P, et al. Hematological studies in children with Down syndrome. Pediatr Hematol Oncol. 1996; 13(3):271-5

74. Lin SJ, Wang JY, Klickstein LB, Chuang KP, Chen JY, Lee JF, et al. Lack of age- associated LFA-1 up-regulation and impaired ICAM-1 binding in lymphocytes from patients with Down syndrome. Clin Exp Immunol. 2001;126(1):54-63

75. Garrison MM, Jeffries H, Christakis DA. () Risk of death for children with Down syndrome and sepsis. J Pediatr. 2005;147(6):748-52

76. Gillespie KM, Dix RJ, Williams AJ, Newton R, Robinson ZF, Bingley PJ, et al. Islet autoimmunity in children with Down's syndrome. Diabetes. 2006;55(11): 3185-8

77. Prasher VP. Screening of medical problems in adults with Down syndrome. Downs Syndr Res Pract. 1994;2:59-66

78. 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(2):767-75

79. Carmichael CL, Majewski IJ, Alexander WS, Metcalf D, Hilton DJ, Hewitt CA, et al. Hematopoietic defects in the Ts1Cje mouse model of Down syndrome. Blood. 2009;113(9):1929-37

80. Alford KA, Slender A, Vanes L, Li Z, Fisher EM, Nizetic D, et al. Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome. Blood. 2010; 115(14):2928-37

81. McLean S, McHale C, Enright H. Hematological abnormalities in adult patients with Down's syndrome. Ir J Med Sci. 2009;178(1):35-8

82. Karlsson B, Gustafsson J, Hedov G, Ivarsson SA, Annerén G. Thyroid dysfunction in Down's syndrome: relation to age and thyroid autoimmunity. Arch Dis Child. 1998;79(3):242-5

83. Loh RK, Harth SC, Thong YH, Ferrante A. Immunoglobulin G subclass deficiency and predisposition to infection in Down's syndrome. Pediatr Infect Dis J. 1990;9(8):547-51

84. Murphy M, Epstein LB. Down syndrome (trisomy 21) thymuses have a decreased proportion of cells expressing high levels of TCR alpha, beta and CD3. A possible mechanism for diminished T cell function in Down syndrome. Clin Immunol Immunopathol. 1990;55(3):453-67

85. Izraeli S. Chromosome copy number and leukemia-lessons from Down's syndrome. Hematology. 2005:10(Suppl. 1):164-6

86. Letourneau A, Santoni FA, Bonilla X, Sailani MR, Gonzalez D, Kind J, et al. Domains of genome-wide gene expression dysregulation in Down's syndrome. Nature. 2014;508(7496):345-50

87. Malinge S, Chlon T, Doré LC, Ketterling RP, Tallman MS, Paietta E, et al. Development of acute megakaryoblastic leukemia in Down syndrome is associated with sequential epigenetic changes. Blood. 2013;122(14):e33-43

88. 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(6):618-23

89. Korbel JO, Tirosh-Wagner T, Urban AE, Chen XN, Kasowski M, Dai L, et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci USA. 2009;106(29):12031-6

90. Malinge S, Bliss-Moreau M, Kirsammer G, Diebold L, Chlon T, Gurbuxani S, et al. Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megaka- ryoblastic leukemia in a murine model of Down syndrome. J Clin Invest. 2012; 122(3):948-62

91. Ng AP, Hyland CD, Metcalf D, Carmichael CL, Loughran SJ, Di Rago L, et al. Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome. Blood. 2010;115(19):3966-9

92. Birger Y, Goldber L, Chlon TM, Goldenson B, Muler I, Schiby G, et al. Perturbation of fetal hematopoiesis in a mouse model of Down syndrome's transient myeloproliferative disorder. Blood. 2013;122(6):988-98

93. Bourquin JP, Subramanian A, Langebrake C, Reinhardt D, Bernard O, Ballerini P, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proc Natl Acad Sci USA. 2006;103(9): 3339-44

94. Gribble SM, Wiseman FK, Clayton S, Prigmore E, Langley E, Yang F, et al. Massively parallel sequencing reveals the complex structure of an irradiated human chromosome on a mouse background in the Tc1 model of Down syndrome. PLoS One. 2013;8(4):e60482

95. Dauphinot L, Lyle R, Rivals I, Dang MT, Moldrich RX, Golfier G, et al. The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome. Hum Mol Genet. 2005;14(3):373-84

96. Aït-Yahya-Graison E, Aubert J, Dauphinot L, Rivals I, Prieur M, Golfier G, et al. Classification of human chromosome 21 gene-expression variations in Down syndrome: impact on disease phenotypes. Am J Hum Genet. 2007;81(3):475-91

97. Conti A, Fabbrini F, D'Agostino P, Negri R, Greco D, Genesio R, et al. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy. BMC Genomics. 2007;8:268

98. Hertzberg L, Betts DR, Raimondi SC, Schäfer BW, Notterman DA, Domany E, et al. Prediction of chromosomal aneuploidy from gene expression data. Genes Chromosomes Cancer. 2007;46(1):75-86

99. Prandini P, Deutsch S, Lyle R, Gagnebin M, Delucinge Vivier C, Delorenzi M, et al. Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. Am J Hum Genet. 2007;81(2):252-63

100. Lockstone HE, Harris LW, Swatton JE, Wayland MT, Holland AJ, Bahn S. Gene expression profiling in the adult Down syndrome brain. Genomics. 2007; 90(6):647-60

101. Gefen N, Binder V, Zaliova M, Linka Y, Morrow M, Novosel A, et al. Hsa-mir-125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53. Leukemia. 2010;24(1):89-96

102. Emmrich S, Rasche M, Schöning J, Reimer C, Keihani S, Maroz A, et al. miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGF and Wnt signaling. Genes Dev. 2014;28(8):858-74

103. Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, et al. Translating dosage compensation to trisomy 21. Nature. 2014;500(7462):296-300

104. Elagib KE, Racke FK, Mogass M, Khetawat R, Delehanty LL, Goldfarb AN. RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood. 2003;101(11):4333-41

105. Rainis L, Toki T, Pimanda JE, Rosenthal E, Machol K, Strehl S, et al. The proto- oncogene ERG in megakaryoblastic leukemias. Cancer Res. 2005;65(17):7596-602

106. Xu G, Kanezaki R, Toki T, Watanabe S, Takahashi Y, Terui K, et al. Physical association of the patient-specific GATA1 mutants with RUNX1 in acute mega- karyoblastic leukemia accompanying Down syndrome. Leukemia. 2006; 20(6):1002-8

107. Yu S, Cui K, Jothi R, Zhao DM, Jing X, Zhao K, et al. GABP controls a critical transcription regulatory module that is essential for maintenace and differentiation of hematopietic stem/progenitor cells. Blood. 2011;117(7):2166-78

108. Garzon R, Pichiorri RF, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, et al. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA. 2006;103(13):5078-83

109. Klusmann JH, Li Z, Böhmer K, Maroz A, Koch ML, Emmrich S, et al. miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia. Gen Dev. 2010;24(5):478-90

110. Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, et al. RUNX1 mutations are frequent in de novo AML with non-complex karyotype and confer an unfavorable prognosis. Blood. 2011;117(8):2348-57


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., . Гемопоэз и лейкозы у пациентов с синдромом Дауна. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2015;14(3):13-33. https://doi.org/10.24287/1726-1708-2015-14-3-13-33

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Roberts I..., Izraeli S... Haematopoietic development and leukaemia in Down syndrome. Pediatric Hematology/Oncology and Immunopathology. 2015;14(3):13-33. (In Russ.) https://doi.org/10.24287/1726-1708-2015-14-3-13-33

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