DNA methylation, DNA hydroxymethylation, MDS, AML, CLL, TETs, DNMTs
Digital Object Identifier (DOI)
Epigenetic dysregulation is present in both myeloid and lymphoid disorders, with important differences reported between myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), on one hand, and chronic lymphocytic leukemia (CLL), on the other. Qualitative differences are reported in MDS/AML with gene fusions (e.g. TET1/LCX) and somatic mutations in epigenetic regulators (e.g. DNMT3A, TET2, IDH1/2), while differences in CLL are predominantly quantitative (e.g. DNMT3A, TET2). Indeed, and as supported by studies in animal models, a defective DNA methylation/demethylation process represents a competitive advantage to the myeloid lineage and an early event in MDS/AML, while in the case of CLL, epigenetic events appear later and are associated with disease progression. Finally, in both MDS/AML and CLL, the focal or global DNA methylation/demethylation process is altered and contributes to disease progression and activity. In conclusion, a better understanding of the epigenetic regulators involved in myeloid/lymphoid differentiation, their localization and the co-recruitment of other proteins at specific DNA target sites, could offer us the possibility to modulate hematopoiesis, and control disease initiation and/or progression.
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Citation / Publisher Attribution
OBM Genetics, v. 2, issue 4, art. 054
Scholar Commons Citation
Bagacean, Cristina; Bordron, Anne; Adrian, Tempescul; Ianotto, Jean Christophe; Guillerm, Gaelle; Brooks, Wesley; Couturier, Marie-Anne; Zdrenghea, Mihnea; Berthou, Christian; and Renaudineau, Yves, "Distinct Mechanisms of Alterations in DNA Methylation/Demethylation Leading to Myelodysplastic Syndromes/Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia" (2018). Chemistry Faculty Publications. 134.