Navigation Links
St. Jude Children's Research Hospital study yields new strategy against high-risk leukemia

MEMPHIS, Tenn., Aug. 29, 2013 /PRNewswire-USNewswire/ -- 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.

The other authors are Jeffrey Morrison, Rhonda Perciavalle, Harpreet Singh and Richard Williams, all formerly of St. Jude; and Jerold Rehg of St. Jude.

The study was supported in part by a grant (HL102175) from the National Institutes of Health, the American Cancer Society and ALSAC.

SOURCE St. Jude Children's Research Hospital
Copyright©2012 PR Newswire.
All rights reserved

Related medicine technology :

1. Humana and Lilly Form Research Collaboration to Improve Health Care Outcomes
2. MEMS in Medical Applications Market is Expected to Reach USD 6.5 Billion Globally in 2019: Transparency Market Research
3. A Young Researcher from Italy Wins this Years "Basel Declaration Award for Education in Animal Research"
4. How Organizations across Industries are Leveraging Employee Insights to Produce Cutting-Edge Market Research
5. Texas Childrens Hospital establishes the Jeffrey Modell Diagnostic & Research Center with a donation from the Jeffrey Modell Foundation
6. X-Ray Devices Market by Volume is Expected to Reach 700.5 Thousand Units Globally in 2018: Transparency Market Research
7. Cancer Research Institute Celebrating 60th Anniversary, Honoring Immunotherapy Leaders
8. Genomics and Proteomics Reagents, Research Kits and Analytical Instruments Market is Expected to Grow to USD 52.3 Billion Globally by 2019: Transparency Market Research
9. Red Carpet Star Studded Celebrity Gala in Partnership with the Michael J. Fox Foundation for Parkinsons Research
10. Cancer Diagnostics Market: Sales Forecasts, 2013 Shares & Competitive Strategies Research Reports
11. Northwestern Medicine Researchers Investigate New Stent Technology to Treat Coronary Artery Disease
Post Your Comments:
(Date:11/24/2015)...  Ascendant Solutions, Inc. (Pink Sheets: ASDS ) ("Ascendant" ... has declared a special 1 percent stock dividend on the ... 14, 2015, to shareholders of record December 7, 2015.  The ... of common stock. --> ... endorsement of our confidence in Ascendant,s growth strategy as well ...
(Date:11/24/2015)... 24, 2015  Figure 1, a free mobile-first network ... cases, has launched a new completely redesigned web version ... allows radiologists, who work primarily on a desktop, to ... with its radiologist user base, Figure 1 is hosting ... North America (RSNA) Annual Meeting. ...
(Date:11/24/2015)... Nov. 24, 2015  Family Rentals, a ... the launch of their newly designed, mobile-responsive website. ... --> Logo - ... --> Now, renting essential items ... vacation, just got a whole lot easier through ...
Breaking Medicine Technology:
(Date:11/24/2015)... ... 2015 , ... Young patients with a wide variety of dental needs can ... S. Lele, who are pediatric dentists in Tucson, AZ . Unlike traditional treatment ... system causes minimal discomfort and bleeding to the patient during treatment and the following ...
(Date:11/24/2015)... ... November 24, 2015 , ... In an article published November ... determine which patients are or are not eligible for bariatric surgery. The article explains ... 40, are more than 100 pounds overweight, or have a BMI of 35 and ...
(Date:11/24/2015)... ... November 24, 2015 , ... The hospitals ... to several aspects of orthopedic care. They have received recognition for excellence from ... orthopedic care. , Becker's Hospital Review selected hospitals for inclusion based on ...
(Date:11/24/2015)... ... 24, 2015 , ... The Trustees, Massachusetts’ largest conservation and ... fees at several of their most popular properties, including Crane Beach in Ipswich, ... REI’s Black Friday #OptOutside Campaign. The Trustees encourage families and friends to take ...
(Date:11/24/2015)... ... November 24, 2015 , ... United Benefit Advisors (UBA), the ... Company as its newest Partner Firm. Based in Jefferson City, Missouri, their core ... advisor regardless of whether that client is a business, a family, or an ...
Breaking Medicine News(10 mins):