Scientists track genetic changes in leukemia

By Will Dunham

WASHINGTON (Reuters) - Distinctive genetic changes occur in the cancer cells that trigger relapse in patients with the most common type of childhood cancer, according to a study that may offer new hope for beating the disease.

Writing in the journal Science on Thursday, the scientists described key genetic differences in cancer cells of children with acute lymphoblastic leukemia, or ALL, when they were first diagnosed compared to when they had a relapse.

ALL is a cancer of the blood and bone marrow. Most children with it can be cured, but among those who suffer a relapse only about 30 percent survive.

The genetic changes in the cancer cells in relapsed ALL patients often affected the biological machinery involving white blood cells called B cells as well as tumor suppression genes, the researchers said.

Rarely did the changes affect genes directly involved in regulating responsiveness to cancer drugs, they said.

“If we are to develop new selective and less toxic treatments for leukemia, we have to have a complete understanding of all of the different genetic changes that contribute to leukemia and contribute to this process of relapse,” said Dr. Charles Mullighan of St. Jude Children’s Research Hospital in Memphis, Tennessee, one of the researchers.

“We’ve pinned them down to certain cellular pathways that are important,” Mullighan said in a telephone interview.

The hope is that by unraveling the genetic factors that help determine whether a person suffers a relapse, scientists can create drugs that may disrupt the process.

“That’s our ultimate goal,” Mullighan said.

The researchers compared the genomes of cancer cells of 61 children with ALL when they were initially diagnosed and after they had relapsed.

“The key finding in our work is that in the majority of cases, relapse is arising from a cell already present at the time of diagnosis,” St. Jude’s Dr. James Downing, another of the researchers, said in a statement. “That cell is selected for during treatment and then subsequently emerges as basis for relapse.”

The researchers proposed that there is an ancestral leukemia cell that gives rise to the cell that causes the initial illness and to another cell that later may emerge as the deadlier relapse cell.

Mullighan said the cure rate for children with ALL exceeds 80 percent around the world. But perhaps 20 percent to 25 percent of children with ALL suffer a relapse.

(Editing by Xavier Briand)

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