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 coh...

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Bibliographic Details
Published in:Leukemia & lymphoma 2013-05, Vol.54 (5), p.1028-1035
Main Authors: Koszarska, Magdalena, Bors, Andras, Feczko, Angela, Meggyesi, Nora, Batai, Arpad, Csomor, Judit, Adam, Emma, Kozma, Andras, Orban, Tamas I., Lovas, Nora, Sipos, Andrea, Karaszi, Eva, Dolgos, Janos, Fekete, Sandor, Reichardt, Judit, Lehoczky, Eniko, Masszi, Tamas, Tordai, Attila, Andrikovics, Hajnalka
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Adolescent
Adult
Aged
Aged, 80 and over
Female
Humans
Isocitrate Dehydrogenase - genetics
isocitrate dehydrogenase 1 and 2
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - mortality
Male
Middle Aged
molecular genetics
Mutation
Prognosis
Recurrence
Treatment Outcome
Young Adult
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Summary: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.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2012.736981