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Gene Responsible For Mammary Gland Function, When Mutated Results in Leukemias

According to the investigators at St. Jude Children's Research Hospital it was found that a gene responsible for regulating the normal mammary gland function during nursing can also initiate leukemias. //

This gene results in leukemia only if it undergoes mutation and fuses with another gene. The discovery of the normal function of this gene suggests that drugs used to inhibit the activity of its mutated form might be used in leukemia patients with few serious side effects, the researchers said. A report on this finding appears in the July 19 online posting of the August 6 issue of Molecular and Cellular Biology (MCB). The researchers made their discovery while trying to determine the normal functions of a gene called MKL1 (megakaryoblastic leukemia 1), which is part of a mutation that causes acute megakaryoblastic leukemia (AMKL) in children, according to Stephan Morris, M.D., a member of Pathology and Oncology at St. Jude.

AMKL is a leukemia in which megakaryocytes--the bone marrow cells that normally produce the blood platelets that control blood clotting--reproduce uncontrollably. The leukemia mutation caused by the fusion of MKL1 to the gene RBM15 forms the RBM15-MKL1 fusion gene. AMKL resulting from this mutation usually has only a 20 to 25 percent survival rate. 'MKL1 is particularly interesting because it does not appear to be necessary for the normal development of blood cells,' Morris said. 'Yet when it's fused with RBM15, the resulting mutation causes AMKL.

In addition, our finding that MKL1 plays a very limited role in the body suggests that if a drug were developed for leukemia treatment that prevents its abnormal function, such a drug might have only mild side effects.' Morris is senior author of the MCB paper. MKL1 belongs to a family of three proteins, each of which can bind to a protein called SRF, which in turn binds to genes that contain a DNA sequence (section of a gene) called the SRE, Morris said. SRF then activate
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