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@ARTICLE{Balss:125471,
author = {J. Balss$^*$ and C. Thiede and T. Bochtler$^*$ and J. G.
Okun and M. Saadati$^*$ and A. Benner$^*$ and S. Pusch$^*$
and G. Ehninger and M. Schaich and A. D. Ho$^*$ and A. von
Deimling$^*$ and A. Krämer$^*$ and C. Heilig$^*$},
title = {{P}retreatment d-2-hydroxyglutarate serum levels negatively
impact on outcome in {IDH}1-mutated acute myeloid leukemia.},
journal = {Leukemia},
volume = {30},
number = {4},
issn = {1476-5551},
address = {Basingstoke},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2017-01597},
pages = {782 - 788},
year = {2016},
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.},
keywords = {Biomarkers, Tumor (NLM Chemicals) / Glutarates (NLM
Chemicals) / alpha-hydroxyglutarate (NLM Chemicals) /
Isocitrate Dehydrogenase (NLM Chemicals) / IDH1 protein,
human (NLM Chemicals)},
cin = {G380 / G330 / C060 / L101 / L301},
ddc = {610},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)G330-20160331 /
I:(DE-He78)C060-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)L301-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26582645},
doi = {10.1038/leu.2015.317},
url = {https://inrepo02.dkfz.de/record/125471},
}