Navigation Links
Drug targets hard-to-reach leukemia stem cells responsible for relapses
Date:1/17/2013

Researchers at the University of California, San Diego School of Medicine have discovered that hard-to-reach, drug-resistant leukemia stem cells (LSCs) that overexpress multiple pro-survival protein forms are sensitive and thus vulnerable to a novel cancer stem cell-targeting drug currently under development.

The findings, published in the January 17 online issue of Cell Stem Cell, open the possibility that diseases like chronic myeloid leukemia (CML) and some solid tumor cancers might in combination with other therapies be more effectively treated with this drug, and with a lower chance of relapse.

Led by principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine and director of stem cell research at UC San Diego Moores Cancer Center, the researchers found that a compound called sabutoclax appears to selectively target LSCs that express particular protein isoforms through alternatively splicing, a fundamental process in which a gene is able to code for multiple proteins.

An emerging class of drugs called tyrosine kinase inhibitors (TKI) such as imitinib (Gleevec), gifitinib (Iressa) and sunitinib (Sutent) has become a popular anti-cancer treatment. However, current TKIs are not 100 percent effective. In cases of CML, for example, some LSCs tucked protectively within bone marrow elude destruction, develop resistance to therapy, self-renew and eventually cause the leukemia to dramatically return.

Jamieson and colleagues found that alternative splicing of BCL2 genes, which code for proteins involved in apoptosis or programmed cell death, specifically promoted malignant transformation of dormant white blood cell precursors into "blast crisis" LSCs. The blast crisis is the final phase of CML when overabundant, abnormal white blood cells crowd out healthy cells, causing serious dysfunction.

Of clinical importance, they noted that sabutoclax, which suppresses all BCL2 anti-apoptotic proteins, renders these marrow-dwelling blast crisis LSCs sensitive and more susceptible to TKI-based therapeutics at doses that do not harm normal progenitor cells.

"Our findings show that pan-BCL2 inhibition will be critical for the eradication of cancer stem cells in CML and that there is an essential link between cancer stem cell dormancy, pro-survival BCL2 isoform expression and therapeutic resistance," Jamieson said. "By using a novel pan-BCL2 inhibitor, we may be able to prevent therapeutic resistance by sensitizing malignant stem cell clones to TKIs."

The findings may have implications for treating solid tumor cancers, such as colon, prostate, breast, and brain cancers, noted Daniel J. Goff, the study's first author.

"With many of these tumor types being shown to harbor cancer stem cells, it raises the question of whether BCL2 family expression as well as isoform-switching may be crucial for the maintenance of cancer stem cells in these diseases as well," he said. "If so, they may also be candidates for treatment with a BCL2 inhibitor like sabutoclax."


'/>"/>

Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related medicine news :

1. SMART heart eases heart ache, targets cardiac patients emotional well-being
2. A closer look at PARP-1 reveals potential new drug targets
3. Identity Theft Expert Advises on Why Elders are Targets for Scams and Financial Abuse
4. Gene sequencing project identifies potential drug targets in common childhood brain tumor
5. Celebrex-derived drug targets common childhood bone tumor
6. First-of-its-kind approach nanomedicine design effectively targets cancer with decreased toxicity
7. NIH tools facilitate matching cancer drugs with gene targets
8. Research funding targets bone health
9. Media alert: 24th EORTC - NCI - AACR Symposium Molecular Targets and Cancer Therapeutics
10. Vanderbilt researchers find proteins may point way to new prostate cancer drug targets
11. Study: Vaccine targets malignant brain cancer antigens, significantly lengthens survival
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Drug targets hard-to-reach leukemia stem cells responsible for relapses
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the Mountains ... possible to save lost souls in the Philippines. “The Journey: From the Mountains to ... dedicated teacher of the Bible. She has taught all ages and currently teaches a ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... Leading pediatric ... peers in Washington, D.C., for the 49th Congress of the International Society of ... Vice President of the Center for Cancer and Blood Disorders at Children’s ...
(Date:10/12/2017)... ... 2017 , ... In the United States, single-family home owners ... New York, New Jersey, Massachusetts, Texas, Virginia, Connecticut, and California—the average is $7,000 ... property-tax rates, which contributes to the relatively lower cost of living in places ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... WESTWOOD, Mass. , Oct. 4, 2017  According to the Centers ... by the end of October . PhysicianOne Urgent Care is helping communities ... Westchester, NY , by offering no-cost* flu shots through ... , as mandated by certain health insurance regulations. ... The best time to get a flu shot is by ...
(Date:10/2/2017)... -- Halo Labs announces the European launch of their new low ... MIBio 2017 in Cambridge, U.K on October ... biopharmaceutical samples with unprecedented speed and sensitivity while using far less ... Imaging. ... analysis system ...
(Date:9/27/2017)... NEW YORK , Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), ... solutions, today announced that its MyDario product is expected to appear on ... for when The Dr. Oz Show airs in your area: http://www.doctoroz.com/page/where-watch-dr-oz-show ... The nine-time Emmy award-winning, The Dr. ... ...
Breaking Medicine Technology: