Biological implications of distinctive H3K79me2 patterns in acute myeloid leukemia
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are found in 20-30% of adult acute myeloid leukemia (AML). Wild type IDH1/2 produce a-ketoglutarate (aKG), an important co-factor for many enzymes including DNA, RNA, and histone demethylases. Mutant IDH1/2 gain the ability to reduce aKG and produce the structurally similar 2-hydroxyglutarate (2HG), a competitive inhibitor of aKG. A previously reported consistent epigenetic alternation observed upon introduction of mutant IDH1/2 or treatment with 2HG is an increase in histone 3 lysine 79 di-methylation (H3K79me2). MLL-rearrangements (ML-r), ...
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