The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate Journal Article

   

Authors:	Ward, P. S.; Patel, J.; Wise, D. R.; Abdel-Wahab, O.; Bennett, B. D.; Coller, H. A.; Cross, J. R.; Fantin, V. R.; Hedvat, C. V.; Perl, A. E.; Rabinowitz, J. D.; Carroll, M.; Su, S. M.; Sharp, K. A.; Levine, R. L.; Thompson, C. B.
Article Title:	The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate
Abstract:	The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases with elevated 2HG possessed IDH1 mutations. The remaining cases with elevated 2HG had mutations in IDH2, the mitochondrial homolog of IDH1. These data demonstrate that a shared feature of all cancer-associated IDH mutations is production of the oncometabolite 2HG. Furthermore, AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis. © 2010 Elsevier Inc. All rights reserved.
Keywords:	adult; clinical article; human tissue; aged; acute granulocytic leukemia; gene mutation; human cell; mutation; leukemia, myeloid, acute; nonhuman; disease marker; cell proliferation; gene; tumor cells, cultured; enzyme activity; tumor marker; dna; nucleotide sequence; cellcycle; screening test; mitochondria; humdisease; enzyme active site; isocitrate dehydrogenase; glutarates; mitochondrial respiration; 2 hydroxyglutaric acid; 2 oxoglutaric acid; isocitrate dehydrogenase (nadp); idh1 gene; idh2 gene; isocitrates; ketoglutaric acids
Journal Title:	Cancer Cell
Volume:	17
Issue:	3
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2010-03-16
Start Page:	225
End Page:	234
Language:	English
DOI:	10.1016/j.ccr.2010.01.020
PUBMED:	20171147
PROVIDER:	scopus
PMCID:	PMC2849316
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77649305610&partnerID=40&md5=d3de360e0036e65edcdd39fa0331483c
Notes:	--- - "Cited By (since 1996): 77" - "Export Date: 20 April 2011" - "CODEN: CCAEC" - "Source: Scopus"

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