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First comprehensive DNA study of mast cell leukemia uncovers clues that could improve therapy
Date:12/16/2011

eated differently and been spared the drug's side-effects." Spector hopes that this information might now encourage physicians to screen MCL patients for both KIT mutations.

The second mutation of interest occurs within the MS4A2 gene, which encodes for a protein that is part of a receptor that sits on a mast cell's surface and is required for its survival. The mutation identified by Spector occurs within the region of the protein that is essential both for its presence on the cell's surface, and more importantly, for triggering intracellular signaling by the enzyme Syk kinase. So Spector suspects that the MS4A2 mutation might be an "activating" mutation that may constantly keep the Syk signal in an "on" state, thereby prolonging the mast cell's life and eventually leading to cancer.

"If we prove this to be the case, then our finding could be therapeutically exploited because there already is a drug that blocks Syk signaling that has shown efficacy in a clinical trial for lymphoma," says Spector. She also observes that their findings might have implications beyond MCL. "For example, Syk signaling is also important in another type of immune cell called B cells, so researchers studying B cell cancers might also want to now look for mutations in genes within this pathway to identify patients who might respond to the Syk inhibitor drug," she says.


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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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