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Scientists find drug target for child leukemia

Researchers have identified the cancer stem cells that spawn tumors in the most common form of childhood leukemia.
/ Source: Reuters

British researchers have identified the cancer stem cells that spawn tumors in the most common form of childhood leukemia, and said on Thursday it provided a "bull's eye" target for new drugs.

The rare stem cells are a minute component of the blood, but they self-renew and act like a control center, producing millions of cancerous leukemia cells that overwhelm the normal system, said Tariq Enver, a researcher at the University of Oxford, who worked on the study.

"Our next goal is to target both the pre-leukaemic stem cell and the cancer stem cell itself with new or existing drugs to cure leukemia while avoiding the debilitating and often harmful side effects of current treatments," Enver said.

Stem cells are the body's master cells, the source of all cells and tissue, like brain, blood, heart, bones, muscle and skin. So-called adult stem cells circulate in the body throughout life, providing a source of renewed cells and tissues.

A growing body of research suggests there are also cancer stem cells, and the team which included Mel Greaves of the Institute of Cancer Research in Britain, say they have found such cells that can escape conventional chemotherapy and cause relapse. This makes it critical to root them out.

"It is like chopping down the weeds but not pulling out the roots," Enver told reporters. "It will look good for a while but they will grow back."

Key to the study were identical twin girls — Olivia, who has leukemia, and her healthy sister, Isabella. Studying them allowed the researchers to look back in time to understand the origins of the disease.

The researchers believe two or more genetic mutations cause all childhood leukemia, with the first occurring in the womb and the other early in life. This raised the question why didn't Isabella develop the disease as well.

"By the time a child has leukemia a lot has gone on," Enver said. "We want to know where it starts. Isabella gives us that opportunity to almost look back in time."

Researchers compared cells in the blood of both girls and found Isabella's cells also had the damaged gene TEL-AML1, the first genetic mutation that can cause acute lymphoblastic leukemia.

Then the team, which published its findings in the journal Science, manufactured the master cancer stem cells with the original mutation in a lab and transplanted them into mice.

This showed the mutation can persist in the blood like a ticking time bomb waiting to trigger the disease after a second genetic mutation. For the twins, this means Isabella remains at risk for the same sort of second "hit" that caused her sister to develop leukemia.

The researchers do not know what causes either of the genetic changes, but believe the second could be something as simple as routine infection.