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Mutation in blood stem cells provides clues to cancer development

that cancers use, subverting normal processes and using them for the wrong purpose. The discovery of this mutation means we can look toward interrupting these pathways, systematically, without wiping out the patient's normal blood cells."

PV is diagnosed in approximately 10,000 to 15,000 people in the United States per year, but the disease has a high prevalence, meaning that people suffer from the disease over a long period of time. The major clinical consequence of PV is the development of thrombosis, in part related to the increased viscosity of the blood. The disorder can also lead to scarring of the bone marrow and acute leukemia. Currently, patients are treated by bleeding them (phlebotomy) or administering low-dose chemotherapy. Co-author Jason Gotlib, M.D., M.S., assistant professor of medicine at the Stanford University School of Medicine said, "We now appreciate that the challenge in fighting certain forms of blood cancer is partly due to a reservoir of leukemic stem cells that are resistant to current therapies. The discovery of the JAK2 mutation in stem cells in patients with PV is an important first step in developing treatments which target the earliest population of cells which propagate the disease."

The research also provides more insight into why some patients develop leukemia or other malignancies, while others don't, by identifying determinant cancer genes and the signaling pathways leading to the disease.

"It will tell us more about cancer and how cancer progresses," Jamieson added. "Usually, cancer isn't just there all of a sudden overnight; it develops by a series of mutations."

The next steps are to see how other stem cell functions on this pathway ?such as self-renewal, survival and proliferation, are affected ?and to duplicate this in-vitro research in mouse models. Working with specific inhibitors developed by local pharmaceutical companies, the UCSD and Stanford researchers plan to conduct clinica
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Source:University of California - San Diego


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