Oncotarget

Priority Research Papers:

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 _

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Oncotarget. 2016; 7:26926-26934. https://doi.org/10.18632/oncotarget.8731

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Abstract

Yulin Li1, Anja Deutzmann1, Peter S. Choi1, Alice C. Fan1 and Dean W. Felsher1

1 Division of Oncology, Department of Medicine and Pathology, Stanford University, Stanford, CA, United States of America

Correspondence to:

Dean W. Felsher, email:

Keywords: apoptosis, BIM, targeted therapies, oncogene inactivation

Received: March 18, 2016 Accepted: April 08, 2016 Published: April 14, 2016

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.


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