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MicroRNA Binds Protein to Help Prevent Leukemia Progression

In an international study, researchers have discovered that loss of a particular microRNA (miR-328) appears to be a key factor in causing the progression of the more treatable chronic phase of chronic myelogenous leukemia (CML) to its life-threatening phase known as the “blast crisis” stage. The study indicates that CML progresses when immature white blood cells lose miR-328, trapping the cells in their rapidly growing, immature state. The cells soon fill the bone marrow and spill into the bloodstream, a tell-tale sign that the disease has advanced to the blast crisis stage. "These findings indicate that the loss of miR-328 is probably essential for progression from the chronic phase of the disease to the blast crisis stage," said principal investigator and senior author Dr. Danilo Perrotti of Ohio State University. "Our findings also suggest that maintaining the level of this microRNA might represent a new therapeutic strategy for CML blast crisis patients who do not benefit from targeted agents such as imatinib (Gleevec) and dasatinib (Sprycel)," Dr. Perrotti continued. The study also revealed a new function for microRNAs. Researchers have known for some time that microRNAs help regulate the kinds of proteins that cells produce by base-pairing with mRNA targets. But this study shows, reportedly for the first time, that microRNAs can also attach directly to proteins and alter their function. In this case, miR-328 binds to a protein (hnRNP E2) that normally prevents immature blood cells from maturing. "We believe that it [miR-328] normally acts as a decoy molecule, tying up the protein [hnRNP E2] and enabling the white blood cells to mature as they should," Dr. Perrotti said "These findings may help unravel novel pathways responsible for the initiation and progression of leukemia generally," Dr. Perrotti asserted. The report was published in the March 5, 2010 issue of Cell. [Press release] [Cell abstract]