Abstract
Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of IDH1/2 mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. IDH1mut and IDH2mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1mut (p = 0.022) and lower mRNA expression level of ABCG2 gene (p = 0.006). Overall survival (OS), remission and relapse rates were not different in IDH1mut or IDH2mut vs. IDHneg. IDH1mut and IDH2mut were associated differently with NPM1mut; co-occurrence was observed in 14.3% of IDH1 R132C vs. 70% of R132H carriers (p = 0.02) and in 47.4% of IDH2 R140Q vs. 0% of R172K carriers (p = 0.02). IDH1 R132H negatively influenced OS compared to IDHneg (p = 0.02) or R132C (p = 0.019). Particular amino acid changes affecting the same IDH1 codon influence the clinical characteristics and treatment outcome in AML.
Acknowledgements
The authors would like to thank the late Sarolta Nahajevszky for initiating and coordinating clinical data acquisition and analysis of patients with AML in her lifetime. We would like to thank Horváth Csongorné, Csehné Bánhidi Klára, Petró Péterné and Pfundt Antalné for their technical assistance.
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
This work was supported by grants from OTKA (K69102), OTKA (PF63953), KMOP 1.1.2-07/1-2008-0003 and COST Action BM0801. H.A. and T.I.O. are recipients of a Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences.