Prognostic implications of IDH1rs11554137 and IDH2R140Q SNPs mutations in cytogenetically normal acute myeloid leukemia

Abstract

Background: Mutant isocitrate dehydrogenase (IDH) 1 and 2 alter the epigenetic landscape in acute myeloid leukemia (AML) cells through production of the oncometabolite (R)-2-hydroxyglutarate. Methods: We aimed to determine the prevalence and clinical and prognostic effect of IDH1rs11554137 and IDH2R140Q SNPs mutations, in 80 newly diagnosed cytogenetically normal AML (CN-AML), using real-time polymerase chain reaction (PCR). Results: Heterozygous mutations of IDH1 and IDH2 SNP were detected in 13.8% and 16.3% of patients, respectively. Both mutations were associated with older age, higher platelet count, and shorter overall survival. Survivors showed significantly younger age and lower mean platelet and blast counts, as well as negative IDH1 SNP (p = 0.001, 0.016, 0.002, and 0.003, respectively). Multivariate logistic regression analysis identified high bone marrow blast percentage as an independent prognostic predictor for 6-month mortality (p = 0.014, OR 1.049, 95% CI 1.010-1.090). Conclusion: IDH1/2 SNPs mutations are recurrent events in CN-AML associated with negative prognostic impact, representing a new subgroup for risk stratification and may indicate new treatment options.

Functional Genetic Variants in ATG10 Are Associated with Acute Myeloid Leukemia

“…Moreover, a SNP located in the mutational hotspot of Wilms tumor 1 ( WT1 ) was identified as a novel favorable prognostic marker in cytogenetically normal AML [ 9 ]. The SNP rs11554137 present at the isocitrate dehydrogenase 1 ( IDH1 ) gene, a citric acid cycle enzyme involved in metabolism, was shown to be a negative outcome predictor of AML [ 10 , 11 ]. The presence of IDH1 rs11554137 results in the production of the oncometabolite (R)-2-hydroxyglutarate leading to the poor prognosis of normal karyotype adult AML.…”