Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia

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. IDH1^mut and IDH2^mut were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. IDH1/2^mut was associated with: older age (p = 0.001), higher average platelet count (p = 0.001), intermediate karyotype (p < 0.0001), NPM1^mut (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 IDH1^mut or IDH2^mut vs. IDH^neg. IDH1^mut and IDH2^mut were associated differently with NPM1^mut; 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 IDH^neg (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.

Keywords::

• Acute myeloid leukemia
• isocitrate dehydrogenase 1 and 2
• mutation
• molecular genetics

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.