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Scientists identify key gene that protects against leukemia
Date:4/8/2009

-beta, which reside on the cells' surface and play critical roles in determining cell fate.

"By uncovering this mechanism, we might one day be able to determine the difference between normal HSCs and leukemic stem cells in gene regulatory networks. This could allow us to develop more targeted therapies. These kinds of therapeutic applications are still down the road, but they can happen very quickly in the blood/leukemia field," says Passegu.

Passegu's study represents a turnabout from other research, which has demonstrated that mutated HSC that cause leukemia burn out at a faster rate than normal HSCs. In contrast, this study shows that JunB does not effect the cells' potential for unlimited self-renewal.

The researchers demonstrated this by treating both JunB-deficient mice and control mice with the powerful chemotherapy drug 5-FU, which was given to deplete regenerating HSCs. As expected, JunB-deficient mice consistently displayed higher levels of myeloid lineage than the control group, indicating constant regeneration of a myeloproliferative disease from JunB-deficient HSCs that persisted after treatment. When researchers compared survival rates of the animals during several cycles of treatment, they found little difference between the two groups, indicating that JunB-deficient HSCs do not exhaust faster than the control HSCs.

In tracking the differences between the JunB-deficient mice and the control group, it became apparent to the researchers that purity of HSCs was a key factor in determining the success of engraftment. Initially, the scientists were struck by the disparity in engraftment between the JunB-deficient HSCs and the control HSCs. But with the use of SLAM cells, a highly purified HSC population, they found that the two groups displayed in fact identical engraftment.

This finding may have important ramifications for patients undergoing bone marrow transplants, for leukemia, lymphoma, multiple myeloma an
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert  

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