BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia.
Oncotarget
; 7(19): 26926-34, 2016 May 10.
Article
in En
| MEDLINE
| ID: mdl-27095570
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 BIMin 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oncogenes
/
Apoptosis
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Bcl-2-Like Protein 11
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2016
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA