New research shows that chronic myeloid leukemia (CML) progresses when immature white blood cells lose the miR-328 molecule. The study by a team from Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and published in the March 5th issue of Cell found, as a news release describes, that loss of the molecule traps the cells in a rapidly growing, immature state. The cells soon fill the bone marrow and spill into the bloodstream, which indicates 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 Danilo Perrotti, MD, PhD, Associate Professor of Molecular Virology, Immunology and Medical Genetics.
“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 and dasatinib.”
The study also revealed a new function for microRNA: It has been known that these molecules help regulate the kinds of proteins that cells make, but the new findings show for the first time that microRNA molecules can also attach directly to protein molecules and alter their function.
DANILO PERROTTI, MD,...Image Tools
In this case, miR-328 binds to a protein that prevents immature blood cells from maturing. “We believe that it normally acts as a decoy molecule, tying up the protein and enabling the white blood cells to mature as they should,” said Dr. Perrotti, a Leukemia and Lymphoma Society Scholar.
During CML progression, however, the level of miR-328 drops, allowing the protein to be extremely active. This keeps the leukemic white blood cells from maturing and contributes to the transition from the chronic-disease phase to blast crisis phase.
“These findings may help unravel novel pathways responsible for the initiation and progression of leukemia generally,” Dr. Perrotti noted.
The study was supported by funding from the National Cancer Institute and the U.S. Army CML Research Program.
© 2010 Lippincott Williams & Wilkins, Inc.