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GEN News Highlights : Jun 4, 2013

Cancer: Why Some Stem Cells Cause Tumors

Understanding how single stem cells are corrupted to cause tumors could be a boon to scientists studying cancers suspected to have a stem cell origin.

Researchers at the University of Cambridge today show that a single mutation in a leukemia-associated gene—JAK2—diminishes the ability of blood stem cells to make more blood stem cells, but does not affect daughter cells. Further, they note, this JAK2 mutation is found in most patients with myeloproliferative neoplasms—bone marrow diseases characterized by the overproduction of mature blood cells as well as an increased risk of leukemia.

Turning to mathematical and mouse models, the team, led by Cambridge’s David Kent, Ph.D., deconstructed a cellular mechanism that operates in stem cells, though not their progeny.

“Combining mathematical modeling with a large number of single stem cell assays allowed us to predict which cells lose their ability to expand,” Dr. Kent said in a statement. “We were able to reinforce this prediction by testing the daughter cells of single stem cell divisions separately and showing that mutant stem cells more often undergo symmetric division to give rise to two non-stem cells.”

The team now aims to understand the effect acquiring additional mutations has on these cells, which could further highlight how the expansion of these blood stem cells leads to the development of leukemia in patients with myeloproliferative neoplasms.

“Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion” was published June 4 in PLoS Biology.