Isocitrate Dehydrogenase (IDH) Mutations in Hematological Malignancies: Epidemiology, Mechanisms, and Therapeutic Strategies

ABSTRACT

Isocitrate dehydrogenase (IDH) mutation is an important molecular abnormality in hematological malignancies, occurring widely in various disease types such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). IDH mutations promote the occurrence and progression of hematological tumors through mechanisms such as epigenetic modification, affecting metabolism and the immune microenvironment. The prognostic significance of IDH mutations highly depends on factors such as disease subtype and mutation site, presenting complex clinical heterogeneity. However, the optimal application strategy of IDH inhibitors in combination therapy and the systematic response plan for drug resistance mechanisms are still lacking a unified consensus at present. This article systematically reviews the incidence and prognosis of IDH mutations in hematological tumors, the carcinogenic mechanism of IDH mutations, and the drug resistance mechanism of IDH inhibitors. It also discusses the clinical efficacy, safety, and combination therapy strategies of the marketed IDH inhibitors (Ivosidenib and Olutasidenib for IDH1 mutations, and Enasidenib for IDH2 mutations). Moreover, emerging technologies are introduced. This review systematically integrates the basic mechanisms of IDH mutations to the clinical translation of related research progress, aiming to provide theoretical and reference basis for clinical treatment decisions and subsequent basic research.