Navigation Links
St. Jude Children's Research Hospital study yields new strategy against high-risk leukemia
Date:8/29/2013

(Memphis, Tenn. August 29, 2013) St. Jude Children's Research Hospital scientists have identified a protein that certain high-risk acute lymphoblastic leukemia (ALL) cells need to survive and have used that knowledge to fashion a more effective method of killing tumor cells. The findings appear in the August 29 edition of the journal Blood.

The work focused on Philadelphia chromosome-positive ALL (Ph-positive ALL), a high-risk cancer that accounts for about 40 percent of ALL in adults and about 5 percent in children. The disease is named for a chromosomal rearrangement that brings together pieces of the BCR and ABL genes. That leads to production of the BCR-ABL protein, which fuels the unchecked cell growth that is a hallmark of cancer.

In this study, researchers identified the protein MCL1 as the partner in crime of BCR-ABL. MCL1 is one of several proteins that can block the process of programmed cell death known as apoptosis. The body uses apoptosis to eliminate damaged, dangerous or unneeded cells. The research demonstrates that MCL1 is essential for preventing apoptosis of leukemia cells.

Investigators combined drugs that reduce MCL1 levels in leukemia cells with a second drug that targets another protein that inhibits cell death. The pairing increased apoptosis in human leukemia cells growing in the laboratory.

"These findings suggest that disrupting the ability of leukemia cells to produce MCL1 renders those cells vulnerable to other drugs," said corresponding author Joseph Opferman, Ph.D., an associate member of the St. Jude Department of Biochemistry. "That is exciting because we already have drugs like imatinib and other tyrosine kinase inhibitors that reduce MCL1 production in tumor cells, leaving those cells vulnerable to being pushed into death via apoptosis by other drugs already in development."

Tyrosine kinase inhibitors are designed to block the BCR-ABL protein. The drugs have revolutionized treatment of chronic myeloid leukemia (CML), which strikes adults and includes the same chromosomal rearrangement as Ph-positive ALL. But results of TKI treatment were less dramatic for adults and children with Ph-positive ALL, and drug resistance remains a problem.

For this study, researchers combined one of two tyrosine kinase inhibitors, imatinib or dasatnib, with the experimental drug navitoclax. The latter drug disrupts the ability of the proteins BCL-2 and BCL-XL to protect cancer cells from apoptosis. Along with MCL1, BCL-2 and BCL-XL are members of a family of proteins that regulate apoptosis. MCL1, BCL-2 and BCL-XL work to prevent cell death, even cancer cell death, by blocking the activity of proteins that promote the process.

Since MCL1 is elevated in a number of cancers and is associated with cancer-drug resistance, a similar two-drug approach might also enhance the effectiveness of tyrosine kinase inhibitors for treatment of other cancers. "We are very interested in pursuing this strategy," Opferman said.

Earlier discoveries made by the Opferman laboratory revealed that MCL-1 also protects heart health by preventing loss of heart muscle cells through apoptosis. "Together these findings suggest that MCL1 is a relevant target for cancer treatment, but efforts should focus on diminishing the expression of MCL1, rather than completely eliminating its function," said first author Brian Koss, a staff scientist in Opferman's laboratory.

In this study, the investigators showed that MCL1 was required for cancer cell survival throughout the Ph-positive ALL disease process, beginning when white blood cells known as B lymphocytes were transformed from normal to tumor cells.

Scientists showed that deleting Mcl1 from the leukemia cells of mice blocked cancer's progression and turned the mice into long-term survivors.


'/>"/>

Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Residential Nursing Care in the UK Industry Market Research Report Now Updated by IBISWorld
2. Phonak, Starkey and Oticon Prosper in Billion Dollar U.S. Hearing Aids Market as Consumer Attitudes Shift with Improved Technology Reports iData Research
3. Worcester Polytechnic Institute Receives $1.94 Million NIH Grant for Cardiac Regeneration Research
4. Brain Size May Signal Risk of Developing an Eating Disorder, CU School of Medicine Researchers Look at Brain Size and Eating Disorders
5. Researchers Discover a Potential Cause of Autism
6. Univ. of Maryland research could result in new approach to prevent diabetes-induced birth defects
7. St. Jude Childrens Research Hospital scientists identify ALS disease mechanism
8. MEMS Market Biosensors and Nanosensors 2013 Analysis in New Research Report at ReportsnReports.com
9. Minimally Invasive Surgery Market - New Industry Research Report Is Now Available for Pre-Order at Transparency Market Research
10. Performance Health Supports Evidence-Based Practice with Annual Research Meeting -- Collaborative Product Research Enables Evidence-Led Decisions That Benefit Patients
11. VisiVite’s® New AREDS2 Plus+ Gold Formula: The Ultimate Research-Backed Macular Health Supplement
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/17/2017)... ... January 17, 2017 , ... SC&H Group, a leading audit, tax, ... in its IT Advisory Services practice . Rossi is the third technology consulting ... for strategic IT guidance grows, and the practice continues to expand.     , Bringing more ...
(Date:1/17/2017)... ... January 17, 2017 , ... ... offices in Tyler, has announced the latest beneficiary of their thriving community involvement ... nonprofit organization dedicated to fulfilling the dreams of terminally ill patients. Donations to ...
(Date:1/17/2017)... ... January 17, 2017 , ... Twelve (12) years ago the ... Education program forged a relationship built upon the foundation of sports safety. ... of both student members and certified members of the Athletic Trainers’ Society of ...
(Date:1/16/2017)... ... January 16, 2017 , ... Gym Source, America’s leading retailer of premium ... East Hanover, New Jersey. , “We are elated to be opening this new showroom,” ... is designed to give clients a seamless and motivating shopping experience.” , Every fitness ...
(Date:1/16/2017)... (PRWEB) , ... January 16, 2017 , ... ... office , Antoine Dental Center, is currently offering complimentary consultations and financing for ... their teeth examined for bite irregularities and learn about their orthodontic options. Walk-in, ...
Breaking Medicine News(10 mins):
(Date:1/17/2017)... , January 17, 2017 ... 2016;11(Suppl. 1):2-4 ; http://www.touchneurology.com/articles/tailored-temperature-management-neurocritical-care ... ... Published recently in European Neurological ... touchNEUROLOGY, Catherine Amey reports that despite ...
(Date:1/17/2017)... -- Transparency Market Research has released a new market ... Alcohol and Others) Market - Global Industry Analysis, Size, Share, Growth, ... benzaldehyde derivative market was valued at US$ 1.37 Bn in ... expanding at a CAGR of 5.1 % from 2016 to 2024. ... Benzaldehyde derivatives are ...
(Date:1/17/2017)... BUDAPEST, Hungary , Jan. 17, 2017 /PRNewswire/ ... Plc. today announced positive results from Venus II, the second ... and safety of ulipristal acetate in women with abnormal bleeding ... ulipristal acetate is planned for the second half of 2017. ... Venus II supporting the efficacy and safety profile of ulipristal ...
Breaking Medicine Technology: