Reports

Acute myeloid leukemia (AML) is caused by somatic genetic mutations that deregulate hematopoietic cell proliferation and differentiation. In many cases of AML the responsible genetic abnormalities are chromo-somal translocations involving key transcription factors, epigenetic regu-lators, and mediators of cell signaling. However, no translocations are detected in 40 % of cases of AML (1). In such cases of “normal cytoge-netic ” AML (NC-AML) the pathogenic driver mutations are largely unknown. Recent genomic sequencing efforts, however, have identified a num-ber of recurrent mutations in NC-AML that might contribute to leukemogenesis, including mutations in Isocitrate Dehydrogenases 1 and 2 (IDH1 and IDH2) (2). IDH1 and IDH2 are key metabolic enzymes that convert isocitrate to α-ketoglutarate [also called 2-oxoglutarate (2-OG)], which is an essential cofactor for 2-OG-dependent dioxygenases. These enzymes are linked to diverse cellular processes such as adaptation t