TY  - JOUR
AU  - Balss, J.
AU  - Thiede, C.
AU  - Bochtler, T.
AU  - Okun, J. G.
AU  - Saadati, M.
AU  - Benner, A.
AU  - Pusch, Stefan
AU  - Ehninger, G.
AU  - Schaich, M.
AU  - Ho, A. D.
AU  - von Deimling, A.
AU  - Krämer, A.
AU  - Heilig, Christoph
TI  - Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia.
JO  - Leukemia
VL  - 30
IS  - 4
SN  - 1476-5551
CY  - Basingstoke
PB  - Nature Publ. Group
M1  - DKFZ-2017-01597
SP  - 782 - 788
PY  - 2016
AB  - 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.
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Glutarates (NLM Chemicals)
KW  - alpha-hydroxyglutarate (NLM Chemicals)
KW  - Isocitrate Dehydrogenase (NLM Chemicals)
KW  - IDH1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26582645
DO  - DOI:10.1038/leu.2015.317
UR  - https://inrepo02.dkfz.de/record/125471
ER  -