Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations

Ashkan Emadi, Sung Ah Jun, Takashi Tsukamoto, Amir T. Fathi, Mark D. Minden, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

The incidence of mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) in de novo acute myeloid leukemia (AML) is approximately 20%. These mutations result in distinct metabolic characteristics including dependency of cancer cells on glutamine as the main source for α-ketoglutarate, which is consumed by leukemia cells to produce a cancer-derived metabolite, 2-hydroxyglutarate. We sought to exploit this glutamine addiction therapeutically in mutant IDH primary AML cells from patients by measuring cell growth after exposure to a small molecule glutaminase inhibitor, BPTES. We found that BPTES only suppressed the growth of AML cells expressing mutant IDH compared with those expressing wild type IDH. This study lays the groundwork for strategies to target a specific subtype of AML metabolically with IDH mutations with a unique reprogramming of intermediary metabolism that culminates in glutamine dependency of cancer cells for survival.

Original languageEnglish (US)
Pages (from-to)247-251
Number of pages5
JournalExperimental Hematology
Volume42
Issue number4
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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