New Pathway Essential for Blood Stem Cell Turnover Identified

by VR Sreeraman on  September 13, 2007 at 4:54 PM Research News   - G J E 4
New Pathway Essential for Blood Stem Cell Turnover Identified
Researchers have identified a blood formation gene, which, if lost, results in early bone marrow failure.

Dartmouth Medical School cancer geneticists have found that all blood cell production in adults depends on the steady work of this vital gene that if lost can lead to premature bone marrow failure.

Their research reveals an unforeseen role for the gene in sustaining the adult blood-forming system, and opens novel strategies for targeting the gene, which is often involved in a type of childhood leukemia.

"We have identified a new pathway that is essential for blood stem cell turnover," said team leader Dr. Patricia Ernst, adding that the pathway could be exploited for treating a rare but aggressive infant leukaemia.

For the study, the investigators created a mouse model to track the function of a gene called MLL, which stands for Mixed Lineage Leukemia. The gene acts in bone marrow stem cells and controls key aspects of their growth to generate all the mature blood cells. If disrupted, it cannot work properly, and thus allows leukemia to develop.

"MLL is the most commonly affected gene in childhood leukemia in children under a year of age; this particular type of leukemia has one of the worst success rates with the existing cancer therapies," said Ernst.

Previous studies indicated that MLL is crucial for embryonic blood stem cell development, but its role for the adult system was unknown. In their mouse model, the researchers found that bone marrow failure occurred as early as 14 days after they induced the experimental loss of MLL, demonstrating the crucial role of MLL as "necessary for both the development and maintenance of the body's blood supply," according to the researchers.

"We have shown that the adult blood-forming system depends on the continuous actions of MLL," Ernst said.

In addition, with the mouse model, they can begin exploring how to craft new anti-cancer treatments, she pointed out.

"We and other groups can start designing targeted therapies that inhibit cancerous forms of MLL that occur in childhood leukemia and do not affect normal MLL function, which, based on our studies in mice, would be fatal for the patient," she said.

The study is published in the September issue of Cell Stem Cell.

Source: ANI

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