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Molecule treats leukemia by preventing cancer cell repair, Jackson Laboratory scientists report
Date:4/17/2013

Researchers at The Jackson Laboratory have identified a molecule that prevents repair of some cancer cells, providing a potential new "genetic chemotherapy" approach to cancer treatment that could significantly reduce side effects and the development of treatment resistance compared with traditional chemotherapy.

In healthy people, white blood cells called B cells (or B lymphocytes) are a kind of sophisticated tool kit, making antibodies against pathogens or other invaders. In the process of antibody production, B cells turn on the gene known as activation-induced cytidine deaminase (AID), which acts as a sort of molecular scissors that cut the chromosomes within the B cell. This is needed to rearrange pieces of the B-cell chromosomes and produce different "flavors" of antibodies that do different jobs.

But in some cancers this process goes wrong, with AID acting out of control and creating mutations and chromosome rearrangements that make the tumor more aggressive.

Those AID-induced cancers proliferate with help from the cell-repair mechanism known as homologous recombination (HR). Researchers in the laboratory of Associate Professor Kevin Mills, Ph.D., identified a molecule called DIDS (for 4,4'-diisothiocyanatostilbene-2-2'-disulfonic acid) that blocks the DNA repair action in chronic lymphocytic leukemia (CLL), causing the cancer cells to die.

"This treatment affects every cell in the body," Mills says. "But by its mode of action it kills only tumor cells that are expressing AID, yet it is almost entirely harmless to normal, healthy cells."

The research, published in The Journal of Experimental Medicine, is the latest proof of principle for what Mills calls "genetic chemotherapy": using the mechanisms involved in genetic instability in cancer, to cause tumor cell self-destruction.

For the new paper, authors Kristin Lamont, Ph.D., a postdoctoral associate, and Muneer Hasham, Ph.D. an associate
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Contact: Joyce Peterson
joyce.peterson@jax.org
207-288-6058
Jackson Laboratory
Source:Eurekalert

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