Journal Article

DKFZ-2017-01597

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia.

Balss, J. (First author)DKFZ* ; Thiede, C. ; Bochtler, T.DKFZ* ; Okun, J. G. ; Saadati, M.DKFZ* ; Benner, A.DKFZ* ; Pusch, S.DKFZ* ; Ehninger, G. ; Schaich, M. ; Ho, A. D.DKFZ* ; von Deimling, A.DKFZ* ; Krämer, A.DKFZ* ; Heilig, C. (Last author)DKFZ*

2016
Nature Publ. Group Basingstoke

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Please use a persistent id in citations: doi:10.1038/leu.2015.317

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.

Keyword(s): Biomarkers, Tumor ; Glutarates ; alpha-hydroxyglutarate ; Isocitrate Dehydrogenase ; IDH1 protein, human

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Contributing Institute(s):

1. KKE Neuropathologie (G380)
2. KKE Molekulare Hämatologie/Onkologie (G330)
3. Biostatistik (C060)
4. DKTK Heidelberg (L101)
5. DKTK Dresden (L301)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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