Acquired resistance was mediated via diverse mechanisms, including emergence or expansion of AML-related mutations in RTK and 2-HG–restoring pathways (comprising second-site mutations in IDH1 and mutations in IDH2), not mutually exclusive within an individual patient, resulting in increased 2-HG (42). However, co-occurring mutations in ASXL1, RUNX1, TP53 and JAK2 genes, commonly associated with a worse prognosis in AML, did not significantly affect the clinical response rate to single agent ivosidenib (42). This evidence concerns the gene TP53 and acute myeloid leukemia.