Prevalence and Clinical Effect of IDH1 and IDH2 Mutations Among Cytogenetically Normal Acute Myeloid Leukemia Patients

This study aimed to determine the frequencies and clinical impact of isocitrate dehydrogenase (IDH) 1 and IDH2 mutations among Egyptian acute myeloid leukemia (AML) patients. The exon 4 of IDH1 and IDH2 were sequenced for detection of mutations in 211 AML bone marrow samples. The IDH1 and IDH2 mutations were detected in 8.5%, and 10.4% respectively. IDH1 and IDH2 mutations are negative prognostic markers in AML patients. A novel mutation (R132V) was detected in IDH1 in our cohort of AML patients. Background: The frequencies of isocitrate dehydrogenase (IDH) 1 and IDH2 mutations among patients with de novo acute myeloid leukemia (AML) are different among different ethnic groups. The aim of this study was to determine the frequencies of IDH1 and IDH2 mutations among Egyptian AML patients and its effect on patient outcomes. Patients and Methods: This study was conducted in 211 adult patients (104 men; 107 women; age range, 18-68 years) with cytogenetically normal AML. DNA was extracted from bone marrow samples at the time of diagnosis. The exon 4 of IDH1 and IDH2 were amplified using polymerase chain reaction and sequenced for detection of mutations. Results: IDH1 mutations were detected in 18 of 211 AML patients (8.5%) in the form of 8 cases, R132H; 6 cases, R132C; 2 cases, R132S; 1 case, R132G; and 1 case, R132V mutations). IDH2 mutations were detected in 22 of 211 AML patients (10.4%) in the form of 20 cases, R140Q; and 2 cases, R172K mutations. The overall survival after correction for nucleophosmin 1 and fims-related tyrosine kinase internal tandem duplication was significantly shorter in AML patients with the IDH mutation compared with those with wild type (P = .02). Conclusion: IDH1 and IDH2 mutations are negative prognostic markers in AML patients. A novel mutation (R132V) was detected in IDH1 in our cohort of AML patients. We recommend molecular testing for IDH1 and IDH2 mutations for proper risk stratification of AML patients before the start of therapy.