Epigenetic alterations in hematopoietic malignancies Journal Article


Authors: Chung, Y. R.; Schatoff, E.; Abdel-Wahab, O.
Article Title: Epigenetic alterations in hematopoietic malignancies
Abstract: Gene discovery efforts in patients with hematopoietic malignancies have brought to the forefront a series of mutations in genes thought to be involved in the epigenetic regulation of gene transcription. These mutations occur in genes known, or suspected, to play a role in modifying cytosine nucleotides on DNA and/or altering the state of histone modifications. Genes such as ASXL1, DNMT3A, EZH2, IDH1/2, MLL1, and TET2 all have been shown to be mutated and/or translocated in patients with myeloid malignancies. Intriguingly, many of the alterations affecting DNA cytosine modifications in myeloid malignancies (mutations in DNMT3A, IDH1/2, and TET2) have also been found in patients with T-cell lymphomas, and EZH2 mutations appear to be critical in T-cell acute lymphoblastic leukemia development as well. In addition, the discovery of frequent mutations in CREBBP, EP300, EZH2, and MLL2 in B-cell lymphomas suggests that epigenetic alterations play a critical role in lymphomagenesis. The purpose of this review is to present functional evidence of how alterations in these epigenetic modifiers promote hematopoietic transformation. The conclusions drawn from these data are valuable in understanding biological mechanisms and potential therapeutic targets. © The Japanese Society of Hematology 2012.
Keywords: leukemia; unclassified drug; gene translocation; methylation; somatic mutation; frameshift mutation; gene deletion; missense mutation; myeloproliferative disorder; myeloid metaplasia; nonhuman; antineoplastic agent; cell proliferation; allele; gene; gene overexpression; dna methylation; acute lymphoblastic leukemia; carcinogenesis; t cell lymphoma; hematologic malignancy; myelodysplastic syndrome; dna; dna modification; protein processing; transcription regulation; epigenetics; chromatin; histone h3; cancer cell; leukemogenesis; lymphoma; hematopoietic stem cell; large cell lymphoma; point mutation; malignant transformation; loss of function mutation; t cell leukemia; follicular lymphoma; nonsense mutation; polycomb group protein; tet2 gene; notch1 receptor; dna methyltransferase 3a; idh1; copy number variation; asxl1 gene; ezh2 gene; transcription factor ezh2; isocitrate dehydrogenase 1; e1a associated p300 protein; histone modification; cytosine; tet2; idh1 gene; idh2 gene; asxl1; ezh2; bap1; idh2; mll; dnmt3a; cyclic amp responsive element binding protein binding protein; lymphomagenesis; dnmt3a gene; isocitrate dehydrogenase 2; methyltransferase inhibitor; crebbp; ep300; chetocin; epz 004777; gsk 1210151a; gsk 525762a; n (1 benzyl 4 piperidinyl) 2 (hexahydro 4 methyl 1h 1,4 diazepin 1 yl) 6,7 dimethoxy 4 quinazolinamine; crebbp gene; ep300 gene; mll1 gene; mll2 gene
Journal Title: International Journal of Hematology
Volume: 96
Issue: 4
ISSN: 0925-5710
Publisher: Springer Japan KK  
Date Published: 2012-10-01
Start Page: 413
End Page: 427
Language: English
DOI: 10.1007/s12185-012-1181-z
PROVIDER: scopus
PUBMED: 23015417
DOI/URL:
Notes: --- - "Export Date: 3 December 2012" - "CODEN: IJHEE" - "Source: Scopus"
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  1. Young Rock Chung
    47 Chung