Prognostic Impact of Isocitrate Dehydrogenase Enzyme Isoforms IDH1 & IDH2 Mutations in Acute Myeloid Leukemia

Abstract

DH1 & 2 mutations are one of the most common genomic abnormalities which have recently been described in acute myeloid leukemia (AML) patients. Mutant IDH1/2 enzymes have neomorphic activity and catalyze the reduction of ketoglutarate to an oncometabolite, which promotes DNA and histone hypermethylation, altered gene expression, and impaired hematopoietic differentiation. In AML the IDH1 and IDH2 mutations are frequently associated with blastic transformation or aggressive forms. The prognostic significance of mutant IDH (mIDH) is controversial but recent studies have shown that IDH1/2 mutation have prognostic value in AML being associated with shorter patients' survival. The role of specific gene mutations in AML continues to be an area of intense interest, and it is becoming increasingly evident that mutations impacting epigenetic mechanisms, such as mutations in IDH1/2, are likely to dictate both prognosis and potential therapeutic responsiveness in intermediate-risk AML. The aim of the present study was to evaluate the prognostic significance of IDH1&2 gene alterations in an Egyptian cohort of adult patients with denovo AML.