Oncotarget: Oncogene inactivation-induced apoptosis in acute lymphoblastic leukemia
Channel: Oncotarget
Date: 2016-05-26

Oncotarget published "BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia" which reported BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia

ORIGINAL SOURCE - https://www.oncotarget.com/news/pr/oncogene-inactivation-induced-apoptosis-in-acute-lymphoblastic-leukemia/

Dr. Dean W. Felsher from Stanford University, and Founding Editorial Board member of Oncotarget said, "Although cancers evolve through a multistage process with accumulation of both genetic and epigenetic changes, many cancers are dependent on specific driver oncogenes for maintenance of the malignancy"

The inactivation of driver oncogenes in mouse cancer models and human targeted therapy often leads to tumor regression associated with the induction of apoptosis.

The mechanism by which oncogene inactivation induces apoptosis in cancer has not been defined.

More recently, BIM, together with other BCL-2 family proteins, have been implicated in the mechanism of apoptosis and therapeutic sensitivity of BCR-ABL positive cells treated with imatinib, lung adenocarcinoma cells treated with EGFR inhibitors, and breast cancer cells treated with HER2 inhibitors.

By crossing of Eμ-tTA mice with mice carrying different oncogenes controlled by a tetracycline-responsive element, the Oncotarget authors are able to regulate oncogene expression in lymphocytes.

Here they have used these transgenic mouse models driven by different oncogenes to investigate the mechanism by which oncogene inactivation induces apoptosis.

The Felsher Research Team concluded in their Oncotarget Priority Research Paper that the activity of BIM seems to be particularly critical in regulating the balance between pro-apoptotic and pro-survival signals.

Even modest changes in BIM activity can significantly influence tumorigenesis and therapeutic responses of cancer.

An intronic deletion polymorphism that produces a less active form of BIM in chronic myeloid leukemia and lung adenocarcinoma patients leads to therapeutic resistance to tyrosine kinase inhibitors.

Thus, BIM is a central mediator of apoptosis associated with therapeutic responses of cancer.

In particular, activation of BIM-mediated apoptosis pathway using BH3 mimetics may synergize with targeted therapeutics to induce sustained tumor regression.

DOI - https://doi.org/10.18632/oncotarget.8731

Full text - https://www.oncotarget.com/article/8731/text/

Correspondence to - Dean W. Felsher - dfelsher@stanford.edu

Keywords - apoptosis, BIM, targeted therapies, oncogene inactivation

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