Unraveling leukemia's fatal attraction

CHICAGO - Leukemia cells use powerful chemical signals to lure healthy blood-forming stem cells into their cancerous lairs, where they lose their power to make healthy blood cells, US researchers said yesterday.

But by jamming these signals in mice, the team was able to protect the stem cells, called hematopoietic progenitor cells.

If it works in humans, this process could help preserve healthy blood cells in people with leukemia, said Dr. Dorothy Sipkins of the University of Chicago Medical Center, whose study appears in the journal Science.

In prior studies, Sipkins found that leukemia cells and some solid tumors create specific niches in the bone marrow where they multiply and spread.

Healthy blood-making cells also congregate in special bone marrow niches, where they divide and make cells needed to fight infection, control blood clotting, and carry oxygen to the body. Sipkins wanted to find out what happens when the two worlds collide.

Her team developed a way to image both types of cells in mice with acute lymphoblastic leukemia or ALL, a cancer of the white blood cells that mostly affects children.

"We saw that the cells that were previously in happy normal homes were actually so attracted by the malignant niches they were migrating into these tumor cell niches," Sipkins said in a telephone interview.

Her team did some experiments to see how these healthy cells would fare in this new environment.

"We found they were compromised. Their number declines over time and once they were in the malignant niche they couldn't leave it. They were stuck there," she said.

Sipkins said it appears the cancer overproduces a normally expressed molecule called a stem cell factor, which entices normal stem cells into the cancer niche.

"They express it in such a high amount in this malignant niche, the progenitor cells say, 'Wow, I'm going to abandon where I am because this smells delicious to me.' "

When the team blocked the release of this chemical signal with neutralizing antibodies, the blood-making cells went about their normal business.

REUTERS