Epigenetic dysregulation of hematopoietic stem cells and preleukemic state

International Journal of Hematology

Volumn 106, Issue 1, 2017, Pages 34-44

  Kunimoto, Hiroyoshi ^a   Nakajima, Hideaki ^b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b YOKOHAMA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

CHIP; Clonal hematopoiesis; Epigenetic regulators; Hematopoietic stem cells; Preleukemic state

Indexed keywords

ASXL1 PROTEIN; DNA METHYLTRANSFERASE 3A; TEN ELEVEN TRANSLOCATION 2 PROTEIN; TRANSCRIPTION FACTOR; TUMOR PROTEIN; UNCLASSIFIED DRUG; BIOLOGICAL MARKER;

APLASTIC ANEMIA; CLINICAL FEATURE; CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL; EPIGENETICS; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMOGENESIS; MOLECULAR PATHOLOGY; MYELOID LEUKEMIA; NONHUMAN; PRELEUKEMIA; REVIEW; SOMATIC MUTATION; AGE; ANIMAL; CELL TRANSFORMATION; CLONAL EVOLUTION; COMPLICATION; CYTOLOGY; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; LEUKEMIA; METABOLISM; MUTATION; PATHOLOGY; PRECANCER;

AGE FACTORS; ANEMIA, APLASTIC; ANIMALS; BIOMARKERS; CELL TRANSFORMATION, NEOPLASTIC; CLONAL EVOLUTION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; HUMANS; LEUKEMIA; MUTATION; PRECANCEROUS CONDITIONS;

EID: 85019734280     PISSN: 09255710     EISSN: 18653774     Source Type: Journal    
DOI: 10.1007/s12185-017-2257-6     Document Type: Review

References (100)

1. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.
2. Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017;17(1):5–19.
3. Shih AH, Abdel-Wahab O, Patel JP, et al. The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer. 2012;12(9):599–612.
4. Akunuru S, Geiger H. Aging, clonality, and rejuvenation of hematopoietic stem cells. Trends Mol Med. 2016;22(8):701–12.
5. Barr RD, Fialkow PJ. Clonal origin of chronic myelocytic leukemia. N Engl J Med. 1973;289(6):307–9.
6. Adamson JW, Fialkow PJ, Murphy S, et al. Polycythemia vera: stem-cell and probable clonal origin of the disease. N Engl J Med. 1976;295(17):913–6.
7. Champion KM, Gilbert JG, Asimakopoulos FA, et al. Clonal haematopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes. Br J Haematol. 1997;97(4):920–6.
8. Hatakeyama C, Anderson CL, Beever CL, et al. The dynamics of X-inactivation skewing as women age. Clin Genet. 2004;66(4):327–32.
9. Busque L, Patel JP, Figueroa ME, et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet. 2012;44(11):1179–81.
10. Shlush LI, Zandi S, Mitchell A, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33.
11. Xie M, Lu C, Wang J, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472–8.
12. Genovese G, Kähler AK, Rose SA, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–87.
13. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–98.
14. Fuster JJ, MacLauchlan S, Zuriaga MA, et al. Clonal hematopoiesis associated with Tet2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355(6327):842–7.
15. Marsh JC, Ball SE, Cavenagh J, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009;147(1):43–70.
16. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509–19.
17. Kulasekararaj AG, Jiang J, Smith AE, et al. Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome. Blood. 2014;124(17):2698–704.
18. Yoshizato T, Dumitriu B, Hosokawa K, et al. Somatic mutations and clonal hematopoiesis in aplastic anemia. N Engl J Med. 2015;373(1):35–47.
19. Aumann S, Abdel-Wahab O. Somatic alterations and dysregulation of epigenetic modifiers in cancers. Biochem Biophys Res Commun. 2014;455(1–2):24–34.
20. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33.
21. Yan XJ, Xu J, Gu ZH, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet. 2011;43(4):309–15.
22. Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2012;30(7):742–50.
23. Jia D, Jurkowska RZ, Zhang X, et al. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449(7159):248–51.
24. Holz-Schietinger C, Reich NO. The inherent processivity of the human de novo methyltransferase 3A (DNMT3A) is enhanced by DNMT3L. J Biol Chem. 2010;285(38):29091–100.
25. Kim SJ, Zhao H, Hardikar S, et al. A DNMT3A mutation common in AML exhibits dominant-negative effects in murine ES cells. Blood. 2013;122(25):4086–9.
26. Russler-Germain DA, Spencer DH, Young MA, et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell. 2014;25(4):442–54.
27. Tadokoro Y, Ema H, Okano M, et al. De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med. 2007;204(4):715–22.
28. Challen GA, Sun D, Jeong M, et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet. 2011;44(1):23–31.
29. Challen GA, Sun D, Mayle A, et al. Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells. Cell Stem Cell. 2014;15(3):350–64.
30. Xu J, Wang YY, Dai YJ, et al. DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells. Proc Natl Acad Sci USA. 2014;111(7):2620–5.
31. Celik H, Mallaney C, Kothari A, et al. Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic transformation. Blood. 2015;125(4):619–28.
32. Mayle A, Yang L, Rodriguez B, et al. Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation. Blood. 2015;125(4):629–38.
33. Guryanova OA, Lieu YK, Garrett-Bakelman FE, et al. Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells. Leukemia. 2016;30(5):1133–42.
34. Guryanova OA, Shank K, Spitzer B, et al. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat Med. 2016;22(12):1488–95.
35. Patel JP, Gönen M, Figueroa M, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–89.
36. Sehgal AR, Gimotty PA, Zhao J, et al. DNMT3A mutational status affects the results of dose-escalated induction therapy in acute myelogenous leukemia. Clin Cancer Res. 2015;21(7):1614–20.
37. Ono R, Taki T, Taketani T, et al. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res. 2002;62(14):4075–80.
38. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5.
39. Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–3.
40. He YF, Li BZ, Li Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303–7.
41. Guo JU, Su Y, Zhong C, et al. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145(3):423–34.
42. Boorstein RJ, Cummings A Jr, Marenstein DR, et al. Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1. J Biol Chem. 2001;276(45):41991–7.
43. Kunimoto H, McKenney AS, Meydan C, et al. Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells. Blood. 2017 (in press).
44. Valinluck V, Sowers LC. Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 2007;67(3):946–50.
45. Chen Q, Chen Y, Bian C, et al. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature. 2013;493(7433):561–4.
46. Vella P, Scelfo A, Jammula S, et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol Cell. 2013;49(4):645–56.
47. Deplus R, Delatte B, Schwinn MK, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32(5):645–55.
48. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.
49. Langemeijer SM, Kuiper RP, Berends M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41(7):838–42.
50. Abdel-Wahab O, Mullally A, Hedvat C, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7.
51. Jankowska AM, Szpurka H, Tiu RV, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113(25):6403–10.
52. Quivoron C, Couronné L, Della Valle V, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38.
53. Sakata-Yanagimoto M, Enami T, Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5.
54. Lemonnier F, Couronné L, Parrens M, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120(7):1466–9.
55. Asmar F, Punj V, Christensen J, et al. Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma. Haematologica. 2013;98(12):1912–20.
56. Ko M, Huang Y, Jankowska AM, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839–43.
57. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67.
58. Yamazaki J, Taby R, Vasanthakumar A, et al. Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia. Epigenetics. 2012;7(2):201–7.
59. Rasmussen KD, Jia G, Johansen JV, et al. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev. 2015;29(9):910–22.
60. Pronier E, Almire C, Mokrani H, et al. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood. 2011;118(9):2551–5.
61. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19(1):17–30.
62. Wang Y, Xiao M, Chen X, et al. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell. 2015;57(4):662–73.
63. Rampal R, Alkalin A, Madzo J, et al. DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep. 2014;9(5):1841–55.
64. Moran-Crusio K, Reavie L, Shih A, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11–24.
65. Li Z, Cai X, Cai CL, et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood. 2011;118(17):4509–18.
66. Ko M, Bandukwala HS, An J, et al. Ten–Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci USA. 2011;108(35):14566–71.
67. Shide K, Kameda T, Shimoda H, et al. TET2 is essential for survival and hematopoietic stem cell homeostasis. Leukemia. 2012;26(10):2216–23.
68. Kunimoto H, Fukuchi Y, Sakurai M, et al. Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells. Sci Rep. 2012;2:273.
69. Kunimoto H, Fukuchi Y, Sakurai M, et al. Tet2-mutated myeloid progenitors possess aberrant in vitro self-renewal capacity. Blood. 2014;123(18):2897–9.
70. Song SJ, Ito K, Ala U, et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell. 2013;13(1):87–101.
71. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.
72. Lundberg P, Karow A, Nienhold R, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123(14):2220–8.
73. Shih AH, Jiang Y, Meydan C, et al. Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia. Cancer Cell. 2015;27(4):502–15.
74. Muto T, Sashida G, Oshima M, et al. Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders. J Exp Med. 2013;210(12):2627–39.
75. Hatlen MA, Arora K, Vacic V, et al. Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles. J Exp Med. 2016;213(1):25–34.
76. Kameda T, Shide K, Yamaji T, et al. Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator. Blood. 2015;125(2):304–15.
77. Chen E, Schneider RK, Breyfogle LJ, et al. Distinct effects of concomitant Jak2V617F expression and Tet2 loss in mice promote disease progression in myeloproliferative neoplasms. Blood. 2015;125(2):327–35.
78. Zhao Z, Chen L, Dawlaty MM, et al. Combined loss of Tet1 and Tet2 promotes B cell, but not myeloid malignancies, in mice. Cell Rep. 2015;13(8):1692–704.
79. Couronné L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366(1):95–6.
80. Scourzic L, Couronné L, Pedersen MT, et al. DNMT3A(R882H) mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice. Leukemia. 2016;30(6):1388–98.
81. Zhang X, Su J, Jeong M, et al. DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells. Nat Genet. 2016;48(9):1014–23.
82. Scheuermann JC, de Ayala Alonso AG, Oktaba K, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature. 2010;465(7295):243–7.
83. Gelsi-Boyer V, Trouplin V, Adélaïde J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145(6):788–800.
84. Boultwood J, Perry J, Pellagatti A, et al. Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia. 2010;24(5):1062–5.
85. Jankowska AM, Makishima H, Tiu RV, et al. Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood. 2011;118(14):3932–41.
86. Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 2010;70(2):447–52.
87. Metzeler KH, Becker H, Maharry K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN favorable genetic category. Blood. 2011;118(26):6920–9.
88. Thol F, Friesen I, Damm F, et al. Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J Clin Oncol. 2011;29(18):2499–506.
89. Abdel-Wahab O, Adli M, LaFave LM, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012;22(2):180–93.
90. Inoue D, Kitaura J, Togami K, et al. Myelodysplastic syndromes are induced by histone methylation-altering ASXL1 mutations. J Clin Invest. 2013;123(11):4627–40.
91. Wang J, Li Z, He Y, et al. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice. Blood. 2014;123(4):541–53.
92. Abdel-Wahab O, Gao J, Adli M, et al. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med. 2013;210(12):2641–59.
93. Shi H, Yamamoto S, Sheng M, et al. ASXL1 plays an important role in erythropoiesis. Sci Rep. 2016;6:28789.
94. Inoue D, Kitaura J, Matsui H, et al. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS. Leukemia. 2015;29(4):847–57.
95. Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330(6009):1410–3.
96. Bott M, Brevet M, Taylor BS, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668–72.
97. Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet. 2012;44(7):751–9.
98. Dey A, Seshasayee D, Noubade R, et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science. 2012;337(6101):1541–6.
99. LaFave LM, Béguelin W, Koche R, et al. Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med. 2015;21(11):1344–9.
100. Koeffler HP, Leong G. Preleukemia: one name, many meanings. Leukemia. 2017;31(3):534–42.