IDH1 and acute myeloid leukemia: For example, treatment of AML with synthetic small-molecule mutIDH inhibitors leads to a reduction in R-2-HG levels, but resistance to first-generation inhibitors has also emerged.117, 118, 119, 120 A better understanding of how altered metabolism is linked to mechanisms of tumor development in IDH1/2 mutant cancers will therefore support new diagnostic, prognostic, and therapeutic developments.