Author/Authors :
Ward، نويسنده , , Patrick S. and Patel، نويسنده , , Jay and Wise، نويسنده , , David R. and Abdel-Wahab، نويسنده , , Omar and Bennett، نويسنده , , Bryson D. and Coller، نويسنده , , Hilary A. and Cross، نويسنده , , Justin R. and Fantin، نويسنده , , Valeria R. and Hedvat، نويسنده , , Cyrus V. and Perl، نويسنده , , Alexander E. and Rabinowitz، نويسنده , , Joshua D. and Carroll، نويسنده , , Martin and Su، نويسنده , , Shinsan M. and Sharp، نويسنده , , Kim A. and Levine، نويسنده , , Ross L. and Thompson، نويسنده , , Craig B.، نويسنده ,
Abstract :
Summary
matic 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.
