%0 Journal Article
%A Balss, J.
%A Thiede, C.
%A Bochtler, T.
%A Okun, J. G.
%A Saadati, M.
%A Benner, A.
%A Pusch, Stefan
%A Ehninger, G.
%A Schaich, M.
%A Ho, A. D.
%A von Deimling, A.
%A Krämer, A.
%A Heilig, Christoph
%T Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia.
%J Leukemia
%V 30
%N 4
%@ 1476-5551
%C Basingstoke
%I Nature Publ. Group
%M DKFZ-2017-01597
%P 782 - 788
%D 2016
%X 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.
%K Biomarkers, Tumor (NLM Chemicals)
%K Glutarates (NLM Chemicals)
%K alpha-hydroxyglutarate (NLM Chemicals)
%K Isocitrate Dehydrogenase (NLM Chemicals)
%K IDH1 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26582645
%R 10.1038/leu.2015.317
%U https://inrepo02.dkfz.de/record/125471