Such reversal of the effect of complex I inhibition following treatment with mutant IDH1 inhibitor is consistent with the critical role of reductive carboxylation in the adaptive response to IACS-010759 in IDH1-mutant tumours52,53, and increased levels of citrate and other TCA cycle intermediates following treatment of IDH1-mutant AML cell lines;40 such reversal of the IDH1-mutant metabolism may explain the response of only some Pdx models to combination therapy using IACS-01075940. Here, IDH1 is linked to acute myeloid leukemia.