Oncotarget

In The News - Press Releases


Oncotarget: Oncogene inactivation-induced apoptosis in acute lymphoblastic leukemia


FOR IMMEDIATE RELEASE
2020-12-03

Here is the link to an interview with Dr. Felsher about this research on the Oncotarget YouTube Channel

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

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.

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.

Figure 4: The microRNA cluster, miR-17-92, regulates apoptosis in MYC-, RAS- but not BCR-ABL-driven ALL model. A.-C. Expression of individual microRNAs in the miR-17-92 cluster upon inactivation of the driver oncogenes. The expression levels of each microRNA were quantified using real-time PCR and normalized to expression level of endogenous U6 snRNA. D.-F. Apoptosis induction and cell cycle distribution in the control and miR-17-92 expressing tumor cells. Cell cycle distribution was assessed by flow cytometric analysis of propidium iodide-stained cells. Apoptosis was quantified by gating on the sub-G1 populations. Oncogene expression was shut off for three days in the MYC and RAS models and for two days in the BCR-ABL model. The gates for sub-G1 populations are set as indicated. The relative percentage of apoptotic populations is labeled in the top right corner of the plots. For each cell line, only one representative plot is shown. Data for the replicates was further quantified and presented in figure G-I. G.-I. Quantification of sub-G1 populations in the control and miR-17-92 expressing tumor cells. Each time point includes at least three replicates. Data are presented as mean +/- SEM. Student's t test. *p < 0.001. n.s. stands for Not Statistically Significant.

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.

Sign up for free Altmetric alerts about this article

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

About Oncotarget

Oncotarget is a biweekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105



Copyright © 2021 Impact Journals, LLC
Impact Journals is a registered trademark of Impact Journals, LLC