The acquisition of resistance mutations that restore 2-HG levels, and thus maintain 2-HG dependence, has been reported in ∼25% of IDH1-mutant AML patients that developed resistance to Ivosidenib [101], although others report lower incidence rates [32,33], highlighting the need for more studies with larger cohort sizes to better ascertain the true prevalence of isoform switching and second-site mutations. The gene discussed is IDH1; the disease is acute myeloid leukemia.