New discovery may lead to therapy for incurable blood cancer

A recent finding may lead to new treatments for multiple myeloma, an incurable cancer of immune cells called plasma cells that are present in the blood and bone marrow. The research, published in the February issue of Cancer Cell, reveals a frequent and common abnormal cellular event that occurs in about half of all myeloma cases and identifies an attractive target for therapeutic intervention.

A research team led by Dr. Louis M. Staudt from the National Cancer Institute in Bethesda, Maryland examined a cancer-causing gene, or oncogene, called c-maf and the interaction of myeloma cells with other types of cells within the bone marrow. Using a sophisticated genetic screening technique, the researchers found that c-maf was present and elevated in about half of all myeloma cases whereas it was absent from normal plasma cells. The researchers further demonstrated that c-maf increases the production of not only factors that directly promote tumor cell growth but also factors that promote tumor cell growth indirectly by increasing adhesion of pathological tumor cells to other types of cells within the bone marrow. Perhaps most significantly, inhibition of c-maf function in myeloma cells blocked tumor formation in mice.

The researchers conclude that c-maf is both functional and overabundant in close to one half of all myelomas and contributes to the pathology of the disease by stimulating both cell proliferation and attachment to structural elements within the bone marrow. According to Dr. Staudt, “Our results indicate that overproduction of c-maf is one of the most common abnormal events associated with myeloma. Further, our finding that inhibition of c-maf blocks myeloma proliferation and tumor formation makes c-maf an intriguing and exciting novel target for future therapies.”

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Elaine M. Hurt, Adrian Wiestner, Andreas Rosenwald, A.L. Shaffer, Elias Campo, Tom Grogan, P. Leif Bergsagel, W. Michael Kuehl, and Louis M. Staudt: “Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma”

Published in Cancer Cell, February 2004, Volume 5, Number 2, pages 191-200.

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