Using two mouse models and a patient-derived xenotransplantation model, Chaturvedi et al. provided evidence that R-2-HG, but not S-2-HG and αKG, is an oncometabolite in vivo that does not require the mutant IDH1 protein to produce hyperleukocytosis and to accelerate the onset of murine and human leukemia [97]. Here, IDH1 is linked to leukemia.