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Acute myeloid leukemia (AML) is a clonal malignant disease of haematopoietic tissue caused by somatic mutations in genes that control normal cell proliferation and differentiation.The molecular genetic alterations is one of the most important prognostic factors that have been identified in AML and the role of this genetic alterations has been emphasized by the 2008 revised WHO classification of AML like FLT3, NPM1, and CEBPA. The isocitrate dehydrogenases (IDHs) are enzymes that catalyze oxidative decarboxylation of isocitrate into ketoglutarate by using NAD or NADP as a cofactor to yield NADH or NADPH, respectively.

This study aimed to evaluate the clinical impact and prognostic relevance of IDH1 and IDH2 mutations among cytogenetically normal AML patients.

Two hundred and eleven patients were assessed for the presence of IDH1 and IDH2 mutations by sequencing.

IDH1 mutation was detected in 18 out of 211 AML patients (8.5 %) and IDH2 mutation was detected in 22 out of 211 AML patients (10.4 %). The IDH1 mutant cases were more older age, female, with high platelet count (P 0.01), high bone marrow blast cells count (P 0.002) and the NPM1 mutation was more common in wild versus mutated groups (81.1% vs 18.9% respectively with P <0.001). The IDH2 mutation was more common in older age, normal karyotyping (P 0.001), with low WBCs count (P 0.003) and high platelets count (P <0.001). The induction of remission rate wasn’t significantly associated with neither IDH1 nor IDH2 mutation status. Patients with mutant IDH1 showed poor OS versus patients with wild type (6 vs 9 months respectively; P 0.07), however there was no statistically significant relation between IDH2 mutation and OS. In this study, there was 24 patients with CN-AML patients (ie: NPM1 mutation and without FLT3 mutation), IDH1 mutation in this group showed significantly shorter overall survival versus patients with IDH1 wild (5 vs 13 months respectively; P 0.02).

IDH1 and IDH2 mutations occur in 8.5% and 10.4% respectively in AML patients which is a minor subset of the newly diagnosed cases and these mutations have an association with molecular and cytogenetic status. We recommend molecular testing for IDH1 and IDH2 mutations to confirm the role of these mutations as novel genetic markers in risk stratification of AML patients in a larger study.