@article{70818af83c0d4cb99c61247811fdd1be,
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.",
keywords = "CELLCYCLE, DNA, HUMDISEASE",
author = "Ward, {Patrick S.} and Jay Patel and Wise, {David R.} and Omar Abdel-Wahab and Bennett, {Bryson D.} and Coller, {Hilary A.} and Cross, {Justin R.} and Fantin, {Valeria R.} and Hedvat, {Cyrus V.} and Perl, {Alexander E.} and Rabinowitz, {Joshua D.} and Martin Carroll and Su, {Shinsan M.} and Sharp, {Kim A.} and Levine, {Ross L.} and Thompson, {Craig B.}",
note = "Funding Information: We thank Tullia Lindsten, Anthony Mancuso, Scott Olejniczak, and other members of the Thompson Laboratory for technical help, valuable discussion, and critical reading of the manuscript. We thank Cezary Swider and Joy Cannon at the University of Pennsylvania's Stem Cell and Xenograft Core for their assistance in obtaining patient samples, and Jesse Platt for help with structural modeling. We also thank Adriana Heguy of the Geoffrey Beene Translational Oncology Core Facility and Kelly Harris for assistance with sequence analysis. R.L.L. is an Early Career Award recipient of the Howard Hughes Medical Institute and is the Geoffrey Beene Junior Chair at Memorial Sloan-Kettering Cancer Center. This work was supported in part by grants from the NCI and NIH. V.R.F., J.D.R., S.M.S., and C.B.T. are employees or consultants of Agios Pharmaceuticals and have financial interest in Agios. ",
year = "2010",
month = mar,
day = "16",
doi = "10.1016/j.ccr.2010.01.020",
language = "English (US)",
volume = "17",
pages = "225--234",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}