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:2/12/2016)... ... 12, 2016 , ... The aging population and longer life ... care. With that, says Patrick Loughney, president of Longtree & Associates, LLC ... term care environments. His company, which offers prep courses and workshops in long ...
(Date:2/12/2016)... ... , ... Planet Future is a Final Cut Pro X themed ... showcasing pictures, videos as well as text in an exciting cartoon environment. Planet Future ... a beautiful frame overlay. Pixel Film Studios makes editing easy; simply insert media into ...
(Date:2/11/2016)... ... February 12, 2016 , ... Fitbody Personal Training offers ... fun and exciting way to get fit and healthy. Located in Phoenixville, PA, the ... for a class designed for horseback riders who want to lose weight and tone ...
(Date:2/11/2016)... ... February 11, 2016 , ... SPH Analytics announced ... analytics leader’s population health solutions, MDinsight® and IndiGO®, for its primary care clinicians. ... system. Details of the contract were not disclosed. , As the healthcare market ...
(Date:2/11/2016)... ... February 11, 2016 , ... Dr. Sadati’s recent feature in ... Along with performing procedures, the magazine also highlights that Dr. Sadati has pioneered ... of the most common procedures he performs is his natural facelift. “As people ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... , Feb. 12, 2016  Eli Lilly and Company ... Court decided the Alimta® (pemetrexed disodium) vitamin regimen patent would ... the UK, France , Italy ... to dilute the product only with dextrose solution.  ... 2015, the UK Court of Appeal held that Lilly,s patent ...
(Date:2/12/2016)... 2016 Indiso ltd ... ungedeckten medizinischen Bedarf bei Lungen- und Atemwegserkrankungen ... Forschungsprogramms bekannt. Das Programm, das sich mit ... respiratorischen Funktionen und anderer klinischer Parameter. ... das sich auf den ungedeckten medizinischen Bedarf ...
(Date:2/11/2016)... 11, 2016 PRO-DEX, INC. (NasdaqCM: PDEX) today announced ... 31, 2015. The Company also filed its Quarterly Report on ... with the Securities and Exchange Commission today. ... --> --> Net sales ... million, or 95%, to $5.4 million from $2.8 million for ...
Breaking Medicine Technology: