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Scientists find fully differentiated blood cells remain able to switch identity

PHILADELPHIA -- Scientists at the University of Pennsylvania School of Veterinary Medicine have found a new wrinkle in the developmental biology dogma that cell differentiation occurs irreversibly as stem cells give rise to increasingly specialized types of offspring cells. The researchers have shown that certain mouse cells retain an ability to oscillate between very distinct blood cell types -- B-cells and macrophages -- long after what has been commonly regarded as the point of no return.

These latest findings on the phenomenon sometimes referred to as "lineage promiscuity" appear on the Web site of the journal Blood and will be published in the journal's print edition in March 2003.

"This work reveals that seemingly committed cells have more plasticity than we had thought," said senior author Andrei Thomas-Tikhonenko, assistant professor of pathobiology at Penn. "It appears there is at least a small window where terminally differentiated cells vacillate on which identity to adopt. We suspect that this phenomenon is not limited to B-cells and macrophages in mice."

Pushing mature cells into other lineages may offer a new way to replace cells involved in blood diseases and neurodegenerative disorders such as Alzheimer's disease. Scientists also say this approach offers the potential for converting lymphoma cells that are resistant to treatment into more manageable forms of cancer.

"We found that just two genes, EBF and Pax5, are turned off when B-cells are concerted into macrophages; Pax5 is a known oncogene implicated in the growth of B-cell lymphomas," Thomas-Tikhonenko said. "It's possible that by targeting this gene with drugs, we may be able to convert malignant B-cell lymphomas into much less harmful histiocytomas, tumors composed of relatively inactive macrophages."

Previous research has demonstrated that when B-cells are transplanted from an animal into a petri dish, the cells sometimes change into macrophages.
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Contact: Steve Bradt
bradt@pobox.upenn.edu
215-573-6604
University of Pennsylvania
16-Dec-2002


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