1. Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia
- Author
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Angela Feczko, András Kozma, Nóra Meggyesi, János Dolgos, András Bors, Judit Reichardt, Emma Ádám, Tamas Masszi, Judit Csomor, Attila Tordai, Magdalena Koszarska, Tamás I. Orbán, Hajnalka Andrikovics, Nóra Lovas, Andrea Sipos, Sandor Fekete, Eniko Lehoczky, Éva Karászi, and Árpád Bátai
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,IDH1 ,Adolescent ,Biology ,medicine.disease_cause ,Gastroenterology ,IDH2 ,Young Adult ,Recurrence ,Molecular genetics ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Mutation ,Myeloid leukemia ,Karyotype ,Hematology ,Middle Aged ,Prognosis ,Isocitrate Dehydrogenase ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Isocitrate dehydrogenase ,Oncology ,Immunology ,Cohort ,Female ,Nucleophosmin - 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 (p0.0001), 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.
- Published
- 2012
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