Abstract
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of BM myeloid cells with impaired differentiation. Of particular interest mutations is the recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1,and UTX) and DNA methylation (DNMT3A,IDH 1/IDH2,TET2) are recurrently mutated in MDS,providing an important link between genetic and epigenetic alterations in this disease. Ongoing analysis of the seminal AZA-001study has taught many important lessons in the use of DNA methyltransferase (DNMT) inhibitors.Improved survival in patients with high-risk MDS treated with azacitidine extends to patients with any International Working Group-defined hematologic response.New information on the impact of DNMT inhibitors on the immune system and on stem cells will likely lead to novel uses of these drugs in MDS and other hematologic and nonhematologic malignancies. The immunomodulating drug thalidomide and its derivative lenalidomide have been used in the treatment of MDS,principally in lower-risk MDS. Key words: Myelodysplastic syndrome; Genetics; DNA methyltransferase inhibitors; Immunomodulate; American Society of Hematology annual meeting
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