Functional proteomics of the epigenetic regulators ASXL1, ASXL2 and ASXL3: A convergence of proteomics and epigenetics for translational medicine

Expert Review of Proteomics

Volumn 12, Issue 3, 2015, Pages 317-328

  Katoh, Masaru ^a  

^a NATIONAL CANCER CENTER   (Japan)

Author keywords

acute myeloid leukemia; cardiovascular development; colorectal cancer; Forkhead box transcription factor; hepatocellular carcinoma; melanoma; microsatellite instability; myelodysplastic syndrome; ovarian cancer; pancreatic cancer

Indexed keywords

ANDROGEN RECEPTOR; ASXL1 PROTEIN; ASXL2 PROTEIN; ASXL3 PROTEIN; BPTF PROTEIN; CELL NUCLEUS RECEPTOR; DIDO PROTEIN; ESTROGEN RECEPTOR ALPHA; ING1 PROTEIN; KMT2E PROTEIN; MEMBRANE PROTEIN; PHF2 PROTEIN; PHF23 PROTEIN; PHF8 PROTEIN; RETINOBLASTOMA BINDING PROTEIN 2; UNCLASSIFIED DRUG; ASXL1 PROTEIN, HUMAN; ASXL2 PROTEIN, HUMAN; ASXL3 PROTEIN, HUMAN; REPRESSOR PROTEIN; TRANSCRIPTION FACTOR;

AUTISM; BREAST CANCER; CHROMATIN; CHROMOSOME 20Q; CHROMOSOME DUPLICATION; EPIGENETICS; FUNCTIONAL PROTEOMICS; GAIN OF FUNCTION MUTATION; GENE MUTATION; GLIOMA; HEMATOLOGIC MALIGNANCY; HUMAN; LOSS OF FUNCTION MUTATION; MEDICINE; NONHUMAN; OPITZ SYNDROME; PROSTATE CANCER; PROTEIN DOMAIN; REVIEW; SOLID TUMOR; TRANSLATIONAL MEDICINE; UTERINE CERVIX CANCER; ANIMAL; GENETIC EPIGENESIS; GENETICS; METABOLISM; MUTATION; PROTEIN TERTIARY STRUCTURE; PROTEOMICS; TRANSLATIONAL RESEARCH;

ANIMALS; EPIGENESIS, GENETIC; HUMANS; MUTATION; PROTEIN STRUCTURE, TERTIARY; PROTEOMICS; REPRESSOR PROTEINS; TRANSCRIPTION FACTORS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84929580822     PISSN: 14789450     EISSN: 17448387     Source Type: Journal    
DOI: 10.1586/14789450.2015.1033409     Document Type: Review

References (126)

1. Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 2005;1:252-62
2. Yates JR, Ruse CI, Nakorchevsky A. Proteomics by mass spectrometry: approaches, advances, and applications. Annu Rev Biomed Eng 2009;11:49-79
3. Katoh M. Great challenges in molecular medicine: toward personalized medicine. Front Cell Dev Biol 2013;1:1
4. Witze ES, Old WM, Resing KA, et al. Mapping protein post-translational modifications with mass spectrometry. Nat Methods 2007;4:798-806
5. Ewing RM, Chu P, Elisma F, et al. Large-scale mapping of human protein- protein interactions by mass spectrometry. Mol Syst Biol 2007;3:89
6. Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 2012;13:227-32
7. Giri NC, Passantino L, Sun H, et al. Structural investigations of the nickel-induced inhibition of truncated constructs of the JMJD2 family of histone demethylases using X-ray absorption spectroscopy. Biochemistry 2013;52: 4168-83
8. Agyeman A, Jha BK, Mazumdar T, et al. Mode and specificity of binding of the small molecule GANT61 to GLI determines inhibition of GLI-DNA binding. Oncotarget 2014;5:4492-503
9. Chu CH, Wang LY, Hsu KC, et al. KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor. J Med Chem 2014;57: 5975-85
10. Lappano R, Maggiolini M. G protein-coupled receptors: novel targets for drug discovery in cancer. Nat Rev Drug Discov 2011;10:47-60
11. Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med 2009;9:873-86
12. Irvine DA, Copland M. Targeting hedgehog in hematologic malignancy. Blood 2012;119:2196-204
13. Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev 2014;34:280-300
14. Klein T, Tucker J, Holdgate GA, et al. FGFR1 kinase inhibitors: close gegioisomers adopt divergent binding modes and display distinct biophysical signatures. ACS Med Chem Lett 2013;5:166-71
15. Tan L, Wang J, Tanizaki J, et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci USA 2014;111:E4869-77
16. Holliday R. The inheritance of epigenetic defects. Science 1987;238:163-70
17. Berger SL, Kouzarides T, Shiekhattar R, et al. An operational definition of epigenetics. Genes Dev 2009;23:781-3 .. Definition of epigenetics in the 21st century.
18. Katoh M. Cardio-miRNAs and oncomiRNAs: circulating miRNA-based diagnostics for non-cancerous and cancerous diseases. Front Cell Dev Biol 2014;2:61
19. Baylin SB, Jones PA. A decade of exploring the cancer epigenome: biological and translational implications. Nat Rev Cancer 2011;11:726-34 . Review on cancer epigenetics.
20. Simo-Riudalbas L, Esteller M. Cancer genomics identifies disrupted epigenetic genes. Hum Genet 2014;133:713-25 . Review on cancer epigenetics.
21. Ordovás JM, Smith CE. Epigenetics and cardiovascular disease. Nat Rev Cardiol 2010;7:510-19
22. Bravo GM, Lee E, Merchan B, et al. Integrating genetics and epigenetics in myelodysplastic syndromes: advances in pathogenesis and disease evolution. Br J Haematol 2014;166:646-59
23. Di Costanzo A, Del Gaudio N, Migliaccio A, et al. Epigenetic drugs against cancer: an evolving landscape. Arch Toxicol 2014;88:1651-68
24. Rose NR, Woon EC, Kingham GL, et al. Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches. J Med Chem 2010;53:1810-18
25. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012;150:12-27 . Review on cancer epigenetics.
26. Kwa FA, Thrimawithana TR. Epigenetic modifications as potential therapeutic targets in age-related macular degeneration and diabetic retinopathy. Drug Discov Today 2014;19:1387-93
27. Machida YJ, Machida Y, Vashisht AA, et al. The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem 2009;284: 34179-88
28. Dey A, Seshasayee D, Noubade R, et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 2012;337: 1541-6
29. Mayya V, Lundgren DH, Hwang SI, et al. Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2009;2:ra46
30. Dephoure N, Zhou C, Ville-n J, et al. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 2008;105:10762-7
31. Bönisch C, Nieratschker SM, Orfanos NK, et al. Chromatin proteomics and epigenetic regulatory circuits. Expert Rev Proteomics 2008;5:105-19
32. Fisher CL, Berger J, Randazzo F, et al. A human homolog of Additional sex combs, ADDITIONAL SEX COMBS-LIKE 1, maps to chromosome 20q11. Gene 2003;306:115-26
33. Katoh M, Katoh M. Identification and characterization of ASXL2 gene in silico. Int J Oncol 2003;23:845-50
34. Katoh M, Katoh M. Identification and characterization of ASXL3 gene in silico. Int J Oncol 2004;24:1617-22
35. Sinclair DA, Milne TA, Hodgson JW, et al. The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes. Development 1998;125:1207-16
36. Gelsi-Boyer V, Trouplin V, Ade-laïde J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009;145:788-800
37. Hoischen A, van Bon BW, Rodríguez-Santiago B, et al. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat Genet 2011;43:729-31 .. First discovery of germ-line ASXL1 mutations in Bohring-Opitz syndrome.
38. Bainbridge MN, Hu H, Muzny DM, et al. De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome. Genome Med 2013;5:11
39. Katoh M. Functional and cancer genomics of ASXL family members. Br J Cancer 2013;109:299-306 .. Review on ASXL genomics in human diseases.
40. Scheuermann JC, de Ayala Alonso AG, Oktaba K, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 2010;465:243-7 . Report on association of ASXL1 with BAP1.
41. White AE, Harper JW. Emerging anatomy of the BAP1 tumor suppressor system. Science 2012;337:1463-4
42. Cho YS, Kim EJ, Park UH, et al. Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor. J Biol Chem 2006;28: 17588-98 . Report on association of ASXL1 with nuclear receptors and NCOA1.
43. Abdel-Wahab O, Adli M, LaFave LM, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 2012;22:180-93 . Report on association of ASXL1 with EZH2.
44. Lai HL, Wang QT. Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets. PLoS One 2013;8:e73983 . Report on association of ASXL2 with EZH2.
45. Khan FF, Li Y, Balyan A, et al. WTIP interacts with ASXL2 and blocks ASXL2-mediated activation of retinoic acid signaling. Biochem Biophys Res Commun 2014;451:101-6 . Report on association of ASXL2 with WTIP.
46. Avila M, Kirchhoff M, Marle N, et al. Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene. Am J Med Genet A 2013;161:1594-8
47. Scotto L, Narayan G, Nandula SV, et al. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer 2008;47: 755-65
48. De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 2014;515:209-15 .. First discovery of germ-line ASXL3 mutations in autism.
49. Ronald A, Hoekstra RA. Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet B 2011;156: 255-74
50. Russell B, Graham JM Jr. Expanding our knowledge of conditions associated with the ASXL gene family. Genome Med 2013;5:16
51. Gelsi-Boyer V, Brecqueville M, Devillier R, et al. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol 2012;5:12 .. Review on ASXL1 cancer genomics in hematological malignancies.
52. Micol JB, Duployez N, Boissel N, et al. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/ RUNX1-RUNX1T1 chromosomal translocations. Blood 2014;124:1445-9
53. Metzeler KH. ASXL genes and RUNX1: an intimate connection? Blood 2014;124: 1382-3
54. Stephens PJ, Tarpey PS, Davies H, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 2012;486:400-4
55. Grasso CS, Wu YM, Robinson DR, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 2012;487:239-43
56. Williams DS, Bird MJ, Jorissen RN, et al. Nonsense mediated decay resistant mutations are a source of expressed mutant proteins in colon cancer cell lines with microsatellite instability. PLoS One 2010;5: e16012
57. Huether R, Dong L, Chen X, et al. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun 2014;5:3630
58. Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science 2011;333: 1157-60
59. Li M, Zhao H, Zhang X, et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet 2011;43:828-9
60. Balbás-Martínez C, Sagrera A. Carrillo-de- Santa-Pau E, et al. Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat Genet 2013;45: 1464-9
61. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321:1801-6
62. Berger MF, Hodis E, Heffernan TP, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 2012;485:502-6
63. Kanchi KL, Johnson KJ, Lu C, et al. Integrated analysis of germline and somatic variants in ovarian cancer. Nat Commun 2014;5:3156
64. Inoue D, Kitaura J, Togami K, et al. Myelodysplastic syndromes are induced by histone methylation-altering ASXL1 mutations. J Clin Invest 2013;123: 4627-40
65. Park UH, Yoon SK, Park T, et al. Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in adipogenesis via reciprocal regulation of peroxisome proliferator-activated receptor g. J Biol Chem 2011;286:1354-63
66. Park UH, Seong MR, Kim EJ, et al. Reciprocal regulation of LXRa activity by ASXL1 and ASXL2 in lipogenesis. Biochem Biophys Res Commun 2014;443:489-94
67. Evans RM. The nuclear receptor superfamily: a rosetta stone for physiology. Mol Endocrinol 2005;19:1429-38
68. Gadaleta RM, Magnani L. Nuclear receptors and chromatin: an inducible couple. J Mol Endocrinol 2014;52:R137-49
69. Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 2010;24: 1967-2000
70. Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006;354:270-82
71. Moore JT, Collins JL, Pearce KH. The nuclear receptor superfamily and drug discovery. ChemMedChem 2006;1:504-23
72. Hervouet E, Cartron PF, Jouvenot M, et al. Epigenetic regulation of estrogen signaling in breast cancer. Epigenetics 2013;8:237-45
73. Aasland R, Gibson TJ, Stewart AF. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem Sci 1995;20: 56-9
74. Schuettengruber B, Chourrout D, Vervoort M, et al. Genome regulation by polycomb and trithorax proteins. Cell 2007;128:735-45
75. Schwartz YB, Pirrotta V. Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev Genet 2007;8:9-22
76. Li H, Ilin S, Wang W, et al. Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature 2006;442:91-5 . Report on interaction between BPTF-2 plant homeodomain (PHD) finger and H3K4me3.
77. Shi XB, Hong T, Walter KL, et al. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 2006;442:96-9 . Report on interaction between ING2 PHD finger and H3K4me3.
78. Baker LA, Allis CD, Wang GG. PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks. Mut Res 2008;647:3-12
79. Chi P, Allis CD, Wang GG. Covalent histone modifications - miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer 2010;10:457-69 .. Review on PHD fingers in human cancers.
80. Sanchez R, Zhou MM. The PHD finger: a versatile epigenome reader. Trends Biochem Sci 2011;36:364-72 .. Review on PHD finger targets.
81. Li Y, Li H. Many keys to push: diversifying the 'readership' of plant homeodomain fingers. Acta Biochim Biophys Sin 2012;44: 28-39
82. Liu L, Qin S, Zhang J, et al. Solution structure of an atypical PHD finger in BRPF2 and its interaction with DNA. J Struct Biol 2012;180:165-73 . Report on interaction between BRPF2-2 PHD finger and DNA.
83. Liu Z, Li F, Ruan K, et al. Structural and functional insights into the human Börjeson-Forssman-Lehmann syndrome-associated protein PHF6. J Biol Chem 2014;289:10069-83 . Report on interaction between PHF6 PHD finger and DNA.
84. Gatchalian J, Fütterer A, Rothbart SB, et al. Dido3 PHD modulates cell differentiation and division. Cell Rep 2013;4:148-58
85. Ooi SK, Qiu C, Bernstein E, et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 2007;448:714-17
86. Soliman MA, Riabowol K. After a decade of study-ING, a PHD for a versatile family of proteins. Trends Biochem Sci 2007;32: 509-19
87. Boulay G, Rosnoblet C, Guerardel C, et al. Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes. Biochem J 2011;434:333-42
88. Wang GG, Song J, Wang Z, et al. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 2009;459:847-51
89. Vermeulen M, Mulder KW, Denissov S, et al. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 2007;131:58-69
90. Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci 2004;61:2571-87
91. Yang XJ, Ullah M. MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells. Oncogene 2007;26:5408-19
92. Ali M, Hom RA, Blakeslee W, et al. Diverse functions of PHD fingers of the MLL/KMT2 subfamily. Biochim Biophys Acta 2014;1843:366-71
93. Lemak A, Yee A, Wu H, et al. Solution NMR structure and histone binding of the PHD domain of human MLL5. PLoS One 2013;8:e77020
94. Angrand P, Apiou F, Stewart AF, et al. NSD3, a new SET domain-containing gene, maps to 8p12 and is amplified in human breast cancer cell lines. Genomics 2001;74: 79-88
95. Katoh M, Katoh M. Identification and characterization of JMJD2 family genes in silico. Int J Oncol 2004;24:1623-8
96. Berry WL, Janknecht R. KDM4/ JMJD2 histone demethylases: epigenetic regulators in cancer cells. Cancer Res 2013;73:2936-42
97. Labbe- RM, Holowatyj A, Yang ZQ. Histone lysine demethylase (KDM) subfamily 4: structures, functions and therapeutic potential. Am J Transl Res 2014;6:1-15
98. Leurs U, Lohse B, Rand KD, et al. Substrate- and cofactor-independent inhibition of histone demethylase KDM4C. ACS Chem Biol 2014;9:2131-8
99. Klose RJ, Kallin EM, Zhang Y. JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet 2006;7:715-27
100. Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 2007;25:1-14
101. Klein BJ, Piao L, Xi Y, et al. The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers. Cell Rep 2014;6: 325-35
102. Johansson C, Tumber A, Che K, et al. The roles of Jumonji-type oxygenases in human disease. Epigenomics 2014;6:89-120
103. Wen H, Li J, Song T, et al. Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation. J Biol Chem 2010;285: 9322-6
104. Feng W, Yonezawa M, Ye J, et al. PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/ 2 demethylation. Nat Struct Mol Biol 2010;17:445-50
105. Ruthenburg AJ, Allis CD, Wysocka J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 2007;25:15-30 .. Review on H3K4me3-binding PHD fingers.
106. Aravind L, Iyer LM. The HARE-HTH and associated domains: novel modules in the coordination of epigenetic DNA and protein modifications. Cell Cycle 2012;11: 119-31
107. Trelle MB, Jensen ON. Functional proteomics in histone research and epigenetics. Expert Rev Proteomics 2007;4: 491-503
108. Han Y, Garcia BA. Combining genomic and proteomic approaches for epigenetics research. Epigenomics 2013;5:1-14
109. Shih AH, Abdel-Wahab O, Patel JP, et al. The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer 2012;12:599-612
110. Cazzola M, Della Porta MG, Malcovati L. The genetic basis of myelodysplasia and its clinical relevance. Blood 2013;122:4021-34
111. Mehdipour P, Santoro F, Minucci S. Epigenetic alterations in acute myeloid leukemias. FEBS J 2015. [Epub ahead of print]
112. Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28:241-7
113. 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;18:553-67
114. Deb G, Thakur VS, Gupta S. Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond. Epigenetics 2013;8:464-76
115. Zhang Y, Tong T. FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis. Biochem Biophys Res Commun 2014;453(1):172-8
116. Tan J, Yan Y, Wang X, et al. EZH2: biology, disease, and structure-based drug discovery. Acta Pharmacol Sinica 2014;35: 161-74
117. Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature 2010;468:1067-73
118. Simhadri C, Daze KD, Douglas SF, et al. Chromodomain antagonists that target the polycomb-group methyllysine reader protein chromobox homolog 7 (CBX7). J Med Chem 2014;57:2874-83
119. Wagner EK, Nath N, Flemming R, et al. Identification and characterization of small molecule inhibitors of a plant homeodomain finger. Biochemistry 2012;51:8293-306
120. Gough SM, Lee F, Yang F, et al. NUP98-PHF23 is a chromatin-modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD histone reader function. Cancer Discov 2014;4:564-77
121. 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;118:6920-9
122. Baskind HA, Na L, Ma Q, et al. Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx. PLoS One 2009;4:e4750
123. McGinley AL, Li Y, Deliu Z, et al. Additional sex combs-like family genes are required for normal cardiovascular development. Genesis 2014;52:671-86
124. Brezinova J, Sarova I, Buryova H, et al. Fusion of the additional sex combs like 1 and teashirt zinc finger homeobox 2 genes resulting from ider(20q) aberration in a patient with myelodysplastic syndrome. Br J Haematol 2014;164:153-5
125. Nakahata S, Saito Y, Hamasaki M, et al. Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/ lymphoma. Genes Chromosomes Cancer 2009;48:768-76
126. Chinen Y, Taki T, Tsutsumi Y, et al. The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t (8;19) (p11;q13). Genes Chromosomes Cancer 2014;53:299-308