BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia

Yulin Li, Anja Deutzmann, Peter S. Choi, Alice C. Fan, Dean W. Felsher

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Oncogene inactivation in both clinical targeted therapies and conditional transgenic mouse cancer models can induce significant tumor regression associated with the robust induction of apoptosis. Here we report that in MYC-, RAS-, and BCR-ABL-induced acute lymphoblastic leukemia (ALL), apoptosis upon oncogene inactivation is mediated by the same pro-apoptotic protein, BIM. The induction of BIM in the MYC-and RAS-driven leukemia is mediated by the downregulation of miR-17-92. Overexpression of miR-17-92 blocked the induction of apoptosis upon oncogene inactivation in the MYC and RAS-driven but not in the BCR-ABL-driven ALL leukemia. Hence, our results provide novel insight into the mechanism of apoptosis upon oncogene inactivation and suggest that induction of BIM-mediated apoptosis may be an important therapeutic approach for ALL.

Original languageEnglish (US)
Pages (from-to)26926-26934
Number of pages9
JournalOncotarget
Volume7
Issue number19
DOIs
StatePublished - May 10 2016

Keywords

  • Apoptosis
  • BIM
  • Oncogene inactivation
  • Targeted therapies

ASJC Scopus subject areas

  • Oncology

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