Featured Research

from universities, journals, and other organizations

Study yields new strategy against high-risk leukemia

Date:
August 29, 2013
Source:
St. Jude Children's Research Hospital
Summary:
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.

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. Koss, J. Morrison, R. M. Perciavalle, H. Singh, J. E. Rehg, R. T. Williams, J. T. Opferman. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood, 2013; 122 (9): 1587 DOI: 10.1182/blood-2012-06-440230

Cite This Page:

St. Jude Children's Research Hospital. "Study yields new strategy against high-risk leukemia." ScienceDaily. ScienceDaily, 29 August 2013. <www.sciencedaily.com/releases/2013/08/130829145003.htm>.
St. Jude Children's Research Hospital. (2013, August 29). Study yields new strategy against high-risk leukemia. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2013/08/130829145003.htm
St. Jude Children's Research Hospital. "Study yields new strategy against high-risk leukemia." ScienceDaily. www.sciencedaily.com/releases/2013/08/130829145003.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins