Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia: Emerging Options and Pending Questions

摘要

With a combined prevalence of approximately 20%, mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most recurrent genetic abnormalities in newly diagnosed acute myeloid leukemia (AML).1 The high frequency of IDH mutations and the fact that IDH mutations induce a gain in enzymatic activity have led to the development of targeted inhibitors of mutated IDH proteins. These efforts have shown to be successful with the development of several, and clinical approval of 2, small molecules in a matter of years.2,3 In addition to dedicated IDH inhibitors, other modes of targeted AML therapy may be effective in eradicating IDH-mutated AML. Ongoing research is directed toward pinpointing optimal combination strategies of IDH inhibitors with other modalities and toward dissecting factors that determine primary or secondary resistance. In this perspective article, an update on targeting IDH-mutated AML is provided.