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Article: Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China

TitlePrognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China
Authors
KeywordsBiomarker
Prognosis
Issue Date2013
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2013, v. 110, n. 42, p. 17017-17022 How to Cite?
AbstractThe 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 μg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/ DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2- HG plays in leukemogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/342457
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Jiang Han-
dc.contributor.authorChen, Wen Lian-
dc.contributor.authorLi, Jun Min-
dc.contributor.authorLi, Yan-
dc.contributor.authorWu, Song Fang-
dc.contributor.authorChen, Tian Lu-
dc.contributor.authorZhu, Yong Mei-
dc.contributor.authorZhang, Wei Na-
dc.contributor.authorLi, Yang-
dc.contributor.authorQiu, Yun Ping-
dc.contributor.authorZhao, Ai Hua-
dc.contributor.authorMi, Jian Qing-
dc.contributor.authorJin, Jie-
dc.contributor.authorWang, Yun Gui-
dc.contributor.authorMa, Qiu Ling-
dc.contributor.authorHuang, He-
dc.contributor.authorWu, De Pei-
dc.contributor.authorWang, Qin Rong-
dc.contributor.authorYan, Xiao Jing-
dc.contributor.authorYan, Jin Song-
dc.contributor.authorLi, Jian Yong-
dc.contributor.authorWang, Shuai-
dc.contributor.authorHuang, Xiao Jun-
dc.contributor.authorWang, Bing Shun-
dc.contributor.authorJia, Wei-
dc.contributor.authorShen, Yang-
dc.contributor.authorChen, Zhu-
dc.contributor.authorChen, Sai Juan-
dc.date.accessioned2024-04-17T07:03:57Z-
dc.date.available2024-04-17T07:03:57Z-
dc.date.issued2013-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2013, v. 110, n. 42, p. 17017-17022-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/342457-
dc.description.abstractThe 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 μg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/ DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2- HG plays in leukemogenesis.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectBiomarker-
dc.subjectPrognosis-
dc.titlePrognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.1315558110-
dc.identifier.pmid24082129-
dc.identifier.scopuseid_2-s2.0-84885759123-
dc.identifier.volume110-
dc.identifier.issue42-
dc.identifier.spage17017-
dc.identifier.epage17022-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000325634200069-

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