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:4/27/2017)... (PRWEB) , ... April 27, 2017 , ... Plastic Surgery ... , have been asked to present at the upcoming Aesthetic Meeting. Held in San ... 27-May 2. Drs. Furnas and Canales will lend their expertise to the Premier Global ...
(Date:4/26/2017)... ... April 26, 2017 , ... CareSet Labs ... of e-prescribing as measured in Part D Medicare data. The dataset, called PaPR ... either using e-prescribing, faxes or paper. The PaPR (pronounced "paper") data set ...
(Date:4/26/2017)... ... , ... Miami native and local periodontist Dr. John Paul Gallardo ... back in 1991 that this journey would have taken me into so many learning ... Dr. Gallardo has pioneered implant dentistry innovation, evolving into an internationally recognized leader in ...
(Date:4/26/2017)... ... April 26, 2017 , ... MYOLYN, a ... announce that it has received 510(k) clearance from the U.S. Food & Drug ... MyoCycle Pro. , Both devices are stationary cycling systems that use MYOLYN’s patent-pending ...
(Date:4/25/2017)... ... 25, 2017 , ... A stressful work environment can hurt the physical and ... and performance in the workplace. The goal of Clearview Resolution Services has always been ... April, Clearview Resolution Services will be shutting down the office early on Fridays. The ...
Breaking Medicine News(10 mins):
(Date:4/26/2017)... , April 26, 2017 Phoenix Marketing Solutions ( ... year of fulfilling its mission of transforming science into clinical ... scrutinized, Phoenix,s innovative approach supports the ... about the latest advances in science and medicine — which ... was founded in 2002 by Tracy Doyle ...
(Date:4/25/2017)... International plc (NASDAQ: ENDP ) will announce its first-quarter ... team will host a conference call and webcast before the U.S. ... dial-in number to access the call is U.S./ Canada ... Please dial in 10 minutes prior to the scheduled start time. ... will be available from May 9, 2017 at 11:30 a.m. ET ...
(Date:4/24/2017)... UNION CITY, Calif. , April 24, 2017 /PRNewswire/ ... providing durability, grip, protection, and comfort, announces the release ... the Powerform S8+. This most recent example of leading ... high density grip pattern for 200% more tactile grip ... in user protection and durability. With TracTek and a ...
Breaking Medicine Technology: