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TET2: epigenetic safeguard for HSC

Myunggon Ko and Anjana Rao

Article Figures & Data

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  • TET2 mutations in myeloid leukemogenesis. TET2 catalyzes the oxidation of 5mC to 5hmC, 5fC and 5caC in the genome and controls HSC self-renewal and function, presumably by regulating gene expression through effects on DNA methylation. Tet2 deficiency in mice impairs 5mC hydroxylation and leads to skewed differentiation and enhanced self-renewal and repopulating capacity of HSCs, promoting malignant transformation to cause disorders resembling MDS, MPD, or MDS/MPD overlap syndromes including CMML. TET2 mutations frequently coexist with other mutations in a wide spectrum of cancers including leukemias and lymphomas, suggesting that additional genetic alterations cooperate with TET2 mutations in different phases of tumorigenesis such as tumor initiation and progression.