Dynamics of IDH1/2 mutated clones in acute myeloid leukemia challenge their use as universal MRD markers

The interpretation of persistent IDH1/2 mutations in acute myeloid leukemia (AML) remains a matter of debate, particularly in the context of measurable residual disease (MRD) assessment. While IDH1 and IDH2 mutations are well-established therapeutic targets and are readily trackable with high analytical sensitivity, their biological position within clonal hierarchies raises uncertainty about whether their persistence reflects residual leukemia or survival of pre-leukemic clones [ 1 , 2 , 3 ]. This distinction has direct clinical implications, as misclassification of IDH1/2 persistence may lead to inappropriate therapeutic escalation or misinterpretation of remission depth.