April 21 : Researchers at the Ohio State University Comprehensive Cancer Center have identified a specific protein, inactivation of which may offer an effective therapy for leukaemia.

The identified protein called Mcl1 helps keep normal cells healthy, and is involved in the development of the components of the immune system, but it can also help prolong survival of cancer cells. Cells with an overabundance of the protein are also more resistant to anticancer drugs, such as rituximab.

The researchers suggest that a drug that can block the activities of the survival protein may offer an effective treatment for drug-resistant forms of chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL), when used in combination with other drugs.

“Our findings demonstrate that Mcl1 may be an effective target for drugs directed against CLL and ALL. These results give us a rationale for lowering the amount of this protein in CLL cells and suggest that this should enhance the action of rituximab and perhaps other agents as well,” says principal investigator John C. Byrd, professor of internal medicine and director of the hematologic malignancies program.

“We’ve shown that knocking down Mcl1 can, by itself, cause CLL cells to die, and that this effect might enhance the activity of rituximab,” added first author Rehan Hussain, a postdoctoral fellow with Ohio State’s Comprehensive Cancer Center.

During the study, the investigators placed molecules called small interfering RNA (siRNA) inside the cells, and found that the tiny molecules greatly reduced the amount of the survival protein, thereby causing many of the cells to die.

The effect was the same even in cells that came from patients with advanced cancer or from patients with tumours that resisted conventional treatment.

Upon treatment of cells with both siRNA and the drug rituximab, it was noted that the combination killed significantly more leukemia cells than the drug alone.

“Our data indicate that specifically targeting Mcl1 might be effective in the treatment of CLL, particularly when combined with rituximab,” says Byrd.

The study has been published online in online in the journal Clinical Cancer Research. (ANI)