Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia.

ABSTRACT: The genomes of myeloid malignancies are characterized by epigenomic abnormalities. Heterozygous, inactivating ten-eleven translocation 2 (TET2) mutations and neomorphic isocitrate dehydrogenase (IDH) mutations are recurrent and mutually exclusive in acute myeloid leukaemia genomes. Ascorbic acid (vitamin C) has been shown to stimulate the catalytic activity of TET2 in vitro and thus we sought to explore its effect in a leukaemic model expressing IDH1^R132H. Vitamin C treatment induced an IDH1^R132H-dependent reduction in cell proliferation and an increase in expression of genes involved in leukocyte differentiation. Vitamin C induced differentially methylated regions that displayed a significant overlap with enhancers implicated in myeloid differentiation and were enric

SUBMITTER: Mingay M 

PROVIDER: S-EPMC5770587 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature