IDH1 and acute myeloid leukemia: In preclinical mechanistic studies, inhibition of mtIDH1 in primary IDH1mt glioma xenografts grown in mice induced the expression of genes associated with both astrocytic and oligodendrocytic differentiation (GFAP, AQP4, ATP1A2, PTGDS, and ZBTB16), and this effect was associated with reduced repressive H3K9 and H3K27 trimethylation on the promoters of these genes.24,55,56 In addition, mtIDH1/2 inhibition in IDH1/2mt AML cells induces differentiation.