Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia. Issue 5 (May 2013)

• Record Type: Journal Article
• 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
• Is Part Of: Leukemia & lymphoma. Volume 54:Issue 5(2013:May)
• Page Start: 1028
• Page End: 1035
• Publication Date: 2013-05
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2012.736981
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>Mutations of isocitrate dehydrogenase 1 and 2 (<italic>IDH1/2</italic>) are genetic alterations in acute myeloid leukemia (AML). The aim of our study was to investigate the frequency and prognostic effect of <italic>IDH1/2</italic> mutations together followed by an individual analysis of each substitution in a Hungarian cohort consisting of 376 patients with AML. <italic>IDH1</italic><sup>mut</sup> and <italic>IDH2</italic><sup>mut</sup> were mutually exclusive, detected in 8.5% and 7.5% of cases, respectively. <italic>IDH1/2</italic><sup>mut</sup> was associated with: older age (<italic>p</italic> = 0.001), higher average platelet count (<italic>p</italic> = 0.001), intermediate karyotype (<italic>p</italic> < 0.0001), <italic>NPM1</italic><sup>mut</sup> (<italic>p</italic> = 0.022) and lower mRNA expression level of <italic>ABCG2</italic> gene (<italic>p</italic> = 0.006). Overall survival (OS), remission and relapse rates were not different in <italic>IDH1</italic><sup>mut</sup> or <italic>IDH2</italic><sup>mut</sup> vs. <italic>IDH</italic><sup>neg</sup>. <italic>IDH1</italic><sup>mut</sup> and <italic>IDH2</italic><sup>mut</sup> were associated differently with <italic>NPM1</italic><sup>mut</sup>; co-occurrence was observed in 14.3% of <italic>IDH1</italic> R132C vs. 70% of R132H carriers (<italic>p</italic> = 0.02) and in 47.4% of <italic>IDH2</italic> R140Q vs. 0% of R172K carriers (<italic>p</italic> = 0.02). <italic>IDH1</italic> R132H negatively influenced OS compared to <italic>IDH</italic><sup>neg</sup> (<italic>p</italic> = 0.02) or R132C (<italic>p</italic> = 0.019). Particular amino acid changes affecting the same <italic>IDH1</italic> codon influence the clinical characteristics and treatment outcome in AML.</p> </abstract>