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

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