IDH mutations activate Hoxa9/Meis1 and hypoxia pathways in acute myeloid leukemia model mice

Yoko Ogawara, Issay Kitabayashi

研究成果: ジャーナルへの寄稿学術論文査読

1 被引用数 (Scopus)

抄録

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 are frequently observed in acute myeloid leukemia (AML), glioma, and many other cancers. While wild-type IDHs mediate exchanges between isocitrate and α-ketoglutarate (α-KG), mutant IDHs convert α-KG to oncometabolite 2-hydroxyglutarate (2-HG), which causes dysregulation of a set of α-KG-dependent dioxygenases such as TET, histone demethylase and others. Because mutant IDH has no necessary functions in normal cells, inhibitors directed against mutant IDH are not expected to have the side effects as anti-cancer agents. To determine whether mutant IDH enzymes are valid targets for cancer therapy, we created a mouse model of mutant IDH2-dependent AML. By using a combination of AML model mice with cre-loxp, we conditionally deleted mutant IDH2 from AML mice, which resulted in the loss of leukemia stem cells and significantly delayed the progression of AML. These results indicate that mutant IDHs are promising targets for anticancer therapy.

本文言語英語
ページ(範囲)1045-1052
ページ数8
ジャーナル[Rinshō ketsueki] The Japanese journal of clinical hematology
56
8
DOI
出版ステータス出版済み - 01-08-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 医学一般

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