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Researchers find mechanism that may determine early blood cell fate

MADISON - Hematopoietic stem cells, the mother of all blood cells, face a fundamental dilemma in their lives.

Each must either remain a hematopoietic stem cell (HSC) by renewing itself or it must transform into one of eight specialized types of blood cells, such as a red blood cell, a white blood cell or a platelet.

Until recently, scientists didn't know how the essential cells, which exist in limited amounts in the body, decide which direction to go. Now, researchers in the University of Wisconsin Medical School Department of Pharmacology have found a mechanism that might determine what each HSC will be. The mechanism involves an unexpected interaction between two related proteins.

Appearing in the July 11, 2003 issue of the Proceedings of the National Academy of Sciences (online), the study should be of special interest to hematologists treating patients with severe cancer, which can deplete blood cells, or blood disorders such as sickle cell disease, beta thalassemia or alpha thalassemia. One common treatment has been to introduce HSCs into the body, where they produce new blood cells to counteract abnormal blood cells or replace absent blood cells.

In the recent past, most blood specialists extracted HSC from bone marrow, where the cells occur in relatively large numbers; however, the procedure can be difficult on some patients. Today, a growing number of hematologists are extracting HSC much more easily from peripheral blood or umbilical cord blood. But since fewer cells are present in these sources, it would be advantageous to expand the cells to increase their numbers, explained Emery Bresnick, UW Medical School professor of pharmacology and senior author on the study.

"Manipulations to expand stem cell numbers can cause the cells to lose their ability to remain stem cells," Bresnick said. "Any mechanism that tells you how to maintain stem cell status and prevent differentiation is a good target for modulating and im
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Contact: Dian Land
dj.land@hosp.wisc.edu
608-263-9893
University of Wisconsin-Madison
14-Jul-2003


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