Chronic myeloid leukemia (CML) progresses to a life-threatening phase called blast crisis when immature white blood cells lose a molecule called miR-328, according to a team led by scientists at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).
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, a tell-tale sign that the disease has advanced to the blast-crisis stage.
The study is published in the March 5 issue of Cell in a paper titled “miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts.”
The study also revealed that miRNAs can attach directly to proteins and alter their function, a new finding for miRNAs, which are known to regulate what proteins a cell makes. The investigators found that miR-328 bound to a protein that usually 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,” explains principal investigator, Danilo Perrotti, M.D., Ph.D., associate professor of molecular virology, immunology, and medical genetics and a member of OSUCCC-James.
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 indicate that the loss of miR-328 is probably essential for progression from the chronic phase of the disease to the blast-crisis stage,” Dr. Perrotti says.