Leukemia gene normally has mammary gland function

A gene critical for normal mammary gland function during nursing helps trigger highly lethal leukemias when it undergoes a mutation that fuses it to another gene, according to investigators at St. Jude Children's Research Hospital.

The discovery of the gene's normal function and that its only major role involves the mammary glands suggests that drugs that might be developed in the future to treat it could also be given to leukemia patients with few serious side effects.

A report on this finding appears in the July 19 online posting of the August 6 issue of Molecular and Cellular Biology.

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, according to Morris. AMKL resulting from this mutation usually has only a 20-25 percent survival rate.

The other authors include Yi Sun (lead author), Kelli Boyd, Wu Xu, Jing Ma, Carl Jackson, Amina Fu and Zhigui Ma (St. Jude); Jonathan Shillingford, Gertraud Robinson and Lothar Hennighausen (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.); and Johann Hitzler (The Hospital for Sick Children, Toronto, Canada).

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