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Pretreatment d -2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia

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...

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Main Authors: Balß, Jörg (Author) , Bochtler, Tilmann (Author) , Okun, Jürgen G. (Author) , Pusch, Stefan (Author) , Ho, Anthony Dick (Author) , Deimling, Andreas von (Author) , Krämer, Alwin (Author) , Heilig, Christoph E. (Author)
Format: Article (Journal)
Language:English
Published: 2016
In: Leukemia
Year: 2015, Volume: 30, Issue: 4, Pages: 782-788
ISSN:1476-5551
DOI:10.1038/leu.2015.317
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/leu.2015.317
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/leu2015317
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Author Notes:J. Balss, C. Thiede, T. Bochtler, J.G. Okun, M. Saadati, A. Benner, S. Pusch, G. Ehninger, M. Schaich, A.D. Ho, A. von Deimling, A. Krämer and C E. Heilig
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Summary: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 IDHmut 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.
Item Description:Published: 19 November 2015
Gesehen am 29.07.2020
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/leu.2015.317

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