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Protein that promotes survival of stem cells might be key to poor leukemia prognosis

The complex and life-sustaining series of steps by which hematopoietic stem cells (HSC) give rise to all of the body's red and white blood cells and platelets has now been discovered to depend in large part on a single protein called Mcl-1. This finding, from an investigator at St. Jude Children's Research Hospital, is published in the February 18 issue of Science.

Mcl-1 blocks the biochemical cascade of reactions that trigger apoptosis ("cell suicide") of HSCs, according to Joseph Opferman, Ph.D., assistant member of St. Jude Biochemistry. Expression of Mcl-1 thus ensures that HSCs continue to thrive and multiply so they can complete the task of making huge numbers of blood cells. This process is extremely important during the initial development of the blood system before birth. Expression of Mc1-1 is also crucial for maintaining blood cells throughout life as red and white cells and platelets die and must be replaced. HSCs are also needed to rebuild the blood system of patients undergoing chemotherapy and radiation for cancer. Opferman completed work on this project while a member of Stanley Korsmeyer's laboratory at the Dana-Farber Cancer Institute (Boston).

Mcl-1 belongs to the Bcl-2 family of proteins. Some of these family members promote apoptosis, while others prevent it. "Other researchers have previously shown that members of the Bcl-2 family that block apoptosis are involved in regulating the number of HSCs and progenitor cells," Opferman said. "But our study showed for the first time that a single such Bcl-2 family protein--Mcl-1--is essential for promoting the survival of these cells."

Progenitor cells are precursors arising from HSCs; these cells produce daughter cells that become increasingly specialized and then produce specific types of blood cells, such as B lymphocytes--immune cells that produce antibodies.

"Understanding the role of Mcl-1 in apoptosis and how this gene is regulated will help my lab at St. Jude unde
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
23-Feb-2005


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