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Stem cells and leukemia battle for marrow microenvironment
Date:12/18/2008

l as more differentiated, though still primitive, progenitor cells that give rise to the various kinds of blood cells--as they struggled for these coveted niche sites.

One of the first actions of cancer cells, they found, is to settle into these niches, taking over the specialized supportive environments that HPCs need to perform their crucial role.

Within days of taking over a niche, leukemia cells began releasing a chemical signal, called stem cell factor (SCF), which attracts normal stem cells back to sites near their now-captive niche. Within one month, the leukemic cells could induce HPCs to leave even tumor-free niches and migrate to malignant sites.

But when the HPCs arrive, other signals released by leukemic cells interfere with the production of healthy new blood cells. As their microenvironments were taken over, the number of HPCs declined. HPCs also stopped responding to drugs designed to coax them out of the bone marrow and into the blood stream, where they could be harvested and used for transplantation.

Sipkins' team was able to blunt this effect by blocking the release of stem cell factor by tumor cells. When the researchers inhibited stem cell factor, the number of HPCs went back up, as did their ability to migrate out of the bone marrow.

"Our data suggest that therapeutic targeting of SCF may increase the hematopoietic reserve and improve outcomes for bone marrow transplantation and autologous stem cell harvest in the setting of hematopoietic malignancy," the authors conclude.

"This is not a cure for leukemia," Sipkins said, "but it's one more tool. We like to hit cancer from all sides. This approach could potentially boost the immune system's response to the cancer by protecting the HPCs that are the source of mature immune cells. It could also maintain the patient's ability to tolerate treatment and to remain active."

"If human stem cells respond in the same way as mouse cells do,
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Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
Source:Eurekalert

Page: 1 2 3

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