Epigenetics in normal and malignant hematopoiesis: An overview and update 2017

被引:43
作者
Goyama, Susumu [1 ]
Kitamura, Toshio [1 ]
机构
[1] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Tokyo, Japan
基金
日本学术振兴会;
关键词
DNA methylation; epigenetics; hematopoiesis; hematopoietic neoplasms; histone modification; STEM-CELL FUNCTION; B-CELL; DNA METHYLATION; TUMOR-SUPPRESSOR; GENE-EXPRESSION; TET2; MUTATIONS; MYELODYSPLASTIC SYNDROMES; CLONAL HEMATOPOIESIS; MYELOID MALIGNANCIES; HISTONE METHYLATION;
D O I
10.1111/cas.13168
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic regulation in hematopoiesis has been a field of rapid expansion. Genome-wide analyses have revealed, and will continue to identify genetic alterations in epigenetic genes that are present in various types of hematopoietic neoplasms. Development of new mouse models for individual epigenetic modifiers has revealed their novel, sometimes unexpected, functions. In this review, we provide an overview of genetic alterations within epigenetic genes in various types of hematopoietic neoplasms. We then summarize the physiologic roles of these epigenetic modifiers during hematopoiesis, and describe therapeutic approaches targeting the epigenetic modifications. Interestingly, the mutational spectrum of epigenetic genes indicates that myeloid neoplasms are similar to T-cell neoplasms, whereas B-cell lymphomas have distinct features. Furthermore, it appears that the epigenetic mutations related to active transcription are more associated with myeloid/T-cell neoplasms, whereas those that repress transcription are associated with B-cell lymphomas. These observations may imply that the global low-level or high-level transcriptional activity underlies the development of myeloid/T-cell tumors or B-cell tumors, respectively.
引用
收藏
页码:553 / 562
页数:10
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