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Mutation in blood stem cells provides clues to cancer development

A mutation in blood stem cells occurs in patients with a blood disorder called polycythemia vera (PV), scientists at the Moores Cancer Center at the University of California, San Diego (UCSD) and the Institute for Stem Cell Biology and Regenerative Medicine and Comprehensive Cancer Center at Stanford University School of Medicine have confirmed.

The discovery suggests that development of a very specific inhibitor at the stem-cell level, to interfere with the pathway leading to the disease, could improve treatment for the cancer-causing disorder.

According to research published in the April 3-7 early on-line edition of Proceedings of the National Academy of Sciences, patients with PV ?a disease in which the patient's body makes too many red blood cells and which can lead to acute leukemia ?have a mutation expressed in the stem cell, the point at which the body's blood cells become structurally and functionally specialized.

The scientists discovered that a mutation in the JAK2 signaling pathway allows the cells to bypass the body's usual mechanism of red blood-cell production, the binding of the hormone erythropoietin (EPO) to its receptor, a process which normally regulates the production of red blood cells. As a result of this intrinsic defect, the bone marrow produces excessive numbers of red blood cells.

"This discovery is important because if we can pinpoint an inhibitor that directly targets the JAK2 mutant allele, we can fight the disease without inhibiting normal stem cell differentiation. These patients could then still produce normal red blood cells, normal platelets and white blood cells," said Catriona H.M. Jamieson, M.D., Ph.D., assistant professor of medicine and Director for Stem Cell Research at UCSD's Moores Cancer Center.

"The body is very utilitarian," added Jamieson, first author of the study. "There are primal pathways that are important for regenerating cells and tissues, and those are the same pathways
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Source:University of California - San Diego


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