MLL, involved in embyronic blood stem cell development and childhood leukemia, is also essential for the adult blood-forming system.

All blood cell production in adults depends on the gene MLL, which if lost results in early bone marrow failure, according to investigators at Dartmouth Medical School.

Previous studies have indicated that MLL, or mixed lineage leukemia, is critical for embryonic blood stem cell development. In infant leukemia, it has been shown that the chromosome containing MLL breaks and ends up fused to a different gene. The MLL fusion genes likely co-opt normal MLL functions in blood cells, leading to the overproduction of white cells and leukemia.

To find out MLL’s role in adults, the Dartmouth team created a mouse model to track the function of MLL. They found that bone marrow failure occurred as early as 14 days after they induced loss of MLL.

“We have shown that the adult blood-forming system depends on the continuous actions of MLL,” says team leader Patricia Ernst, Ph.D., assistant professor of genetics. With the new mouse model, “us 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.”

These findings are reported in the September issue of Cell Stem Cell.

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