Details

Autor(en) / Beteiligte

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

Titel

The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate

Ist Teil von

• Cancer cell, 2010-03, Vol.17 (3), p.225-234

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2010

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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. ► All IDH mutations reported in cancer share a common neomorphic enzymatic activity ► Both wild-type IDH1 and IDH2 are required for cell proliferation ► IDH2 R140Q mutations occur in 9% of AML cases ► Overall, IDH2 mutations appear more common than IDH1 mutations in AML