| Literature DB >> 26582645 |
J Balss1,2, C Thiede3, T Bochtler4,5, J G Okun6, M Saadati7, A Benner7, S Pusch1,2, G Ehninger3, M Schaich3, A D Ho4, A von Deimling1,2, A Krämer4,5, C E Heilig4,5.
Abstract
Mutations in isocitrate dehydrogenases (IDHs) 1 and 2 frequently occur in acute myeloid leukemia (AML) and result in the production of the oncometabolite d-2-hydroxyglutarate (D2HG). D2HG has been shown to promote leukemogenesis even in the absence of mutated IDH, but the prognostic significance of pretreatment serum D2HG levels in patients with IDH-mutated AML is unclear. We measured D2HG serum levels in 84 patients with IDH-mutated AML treated in the prospective, randomized multicenter AML2003 trial of the German Study Alliance Leukemia. Multivariate Cox regression showed D2HG levels to negatively impact on event-free survival (EFS) as a continuous variable in the entire IDH(mut) cohort (P=0.04), with no effect on overall survival (OS). In a subgroup analysis, the negative impact of D2HG on EFS was found to be restricted to patients with mutations in IDH1 (P=0.003), adjusted for age, leukocyte count, serum lactate dehydrogenase and European LeukemiaNet risk score. We thus conclude that pretreatment D2HG serum levels may yield prognostic information in patients with IDH1-mutated, but not in IDH2-mutated AML, possibly due to different subcellular localizations of IDH1 and IDH2.Entities:
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Year: 2015 PMID： 26582645 DOI： 10.1038/leu.2015.317
Source DB: PubMed Journal: Leukemia ISSN： 0887-6924 Impact factor: 11.528