Unusual RNAs Linked To Chronic Leukemia, May Help Treat It

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Chronic Lymphocytic Leukemia Treatment

A new and unusual class of genes plays an important role in the development of chronic lymphocytic leukemia (CLL), according to new research here. At the same time, these genes may provide a new form of therapy for the disease.

Chronic Lymphocytic Leukemia strikes some 9,700 Americans annually, making it the most common adult leukemia in the world.

The study found that the loss of two genes for producing small molecules known as microRNAs enables damaged cells to survive, rather than normally self-destructing before they become cancerous.

"Our findings show that microRNA genes are involved in the development of Chronic Lymphocytic Leukemia," says principal investigator Carlo M. Croce, professor and chair, Department of Molecular Virology, Immunology and Medical Genetics at Ohio State, and director of the Human Cancer Genetics Program at the OSU Comprehensive Cancer Center. "They also strongly suggest that microRNAs might be used therapeutically for CLL and probably other cancers."

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The research is published online in the current issue of the Proceedings of the National Academy of Science.

The two microRNA genes are known as miR-15 and miR-16. Earlier work led by Croce showed that about 65 percent of Chronic Lymphocytic Leukemia patients have cancer cells that show the loss of, or damage to, these genes.

This study shows that the two microRNAs interact closely with a protein known as Bcl-2. That protein stops cells from self-destructing through a natural process known as apoptosis. (In 1984, Croce led the research that discovered the Bcl-2 gene.)

In Chronic Lymphocytic Leukemia cells and cells from other kinds of cancer, the Bcl-2 protein is present in abnormally high levels. This prevents the malignant cells from self-destructing as they should and leads to tumor growth. In about 95 percent of Chronic Lymphocytic Leukemia cases, scientists did not know why Bcl-2 was present at high levels. The current paper now answers that.

Croce and his colleagues discovered that the miR-15 and miR-16 microRNAs play an important role in controlling Bcl-2 levels, normally keeping them low. When the two microRNA genes are lost

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