St. Jude identifies genomic causes of a certain type of leukem...(and be responsible for relapse. Ac...)

According to the researchers, the relapse-related genetic changes commonly disrupted the machinery by which white blood cells called B cells mature and proliferate. Importantly, the relapse-related genetic changes only infrequently involved genes directly regulating the responsiveness to anti-cancer drugs.

The analysis also indicated that in most cases, the cancer cells responsible for relapse were related to those that originally gave rise to the cancer. Those relapse cells were present at low levels at diagnosis, the scientists' analysis indicated. However, in a few cases, the relapse cells evolved from genetically distinct cells, indicating that the relapsed leukemia was actually an entirely new cancer.

"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," said James Downing, M.D., St. Jude Scientific Director, chair of the Department of Pathology and the paper's senior author. "That cell is selected for during treatment and then subsequently emerges as basis for relapse."

"The second key point is that we have found a large number of new genetic alterations that had not been previously identified as new targets of copy number changes at the time of relapse," Mullighan added.

Mullighan emphasized that the findings do not mean immediate treatments for ALL relapse. "But, this is a very important starting point because we have identified several key pathways that are the most common targets of new genetic changes at the time of relapse," he said.

Identification of these relapse pathways will lead to understanding of the biological machinery of relapse, and ultimately to drugs that target that machinery. Such studies of the relapse machinery are now underway at St. Jude.

In other further studies, the researchers are also looking for other relapse-related genetic alterations besides copy num
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