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Every year, 13,000 Americans are diagnosed with multiple myeloma, an incurable type of blood cancer in which malignant plasma cells proliferate in the bone marrow. New research has identified a cellular abnormality that turns out to be extremely common in patients afflicted with this disease and might prove a target for future therapies.
Using DNA microarray technology, Louis Staudt of the National Cancer Institute and his colleagues profiled the genes associated with multiple myeloma and observed that an oncogene called c-maf was overexpressed in half of all the myeloma cell lines they examined. In subsequent experiments, the team found that inhibiting this oncogene in immunodeficient mice suppressed tumor formation. To tease out c-maf's specific role in multiple myeloma, the researchers then studied two proteins regulated by the oncogene. "Our data suggests this oncogene delivers a double-whammy to the cells," Staudt explains, by upregulating the two downstream proteins. One of these proteins, cyclin D2, increases plasma cell proliferation; the other, integrin beta 7, encourages the cells to adhere to one another, which enhances survival. (In the case of multiple myeloma, cancerous cells stick to normal cells.) Thus armed with a surplus of cyclin D2 and integrin beta 7, the cancerous cells are better at both spreading and persisting than are their normal counterparts. These findings come as a surprise. "Whereas most oncogenes render the tumor cell independent of external signals for proliferation and survival," the researchers write, "c-maf defines a class of oncogenes that enhance interactions" between normal cells and cancerous ones.
Why c-maf is overexpressed in a distinct subset of myeloma cases is not known, but the study, published in the current issue of the journal Cancer Cell, provides insight into how the genetics of multiple myeloma affect the mechanisms of the disease. "The drugs we use [for treatment] will ultimately target oncogenic abnormalities," Staudt notes. "Drugs targeting c-maf will have no value for half of multiple myeloma patients, but according to our experimental data will help the other half." --Alla Katsnelson
