Myelomas Lacking Master Regulator Gene Die

Death occurs regardless of underlying genetic abnormalities

MONDAY, June 23 (HealthDay News) -- Myelomas lacking a protein that acts as a master regulator of gene expression die, regardless of the underlying genetic abnormalities, according to research published online June 22 in Nature.

Arthur L. Shaffer, Ph.D., from the National Institutes of Health in Bethesda, Md., and colleagues used a genetic method to screen for proteins in myeloma cells that were involved in proliferation and/or survival.

The researchers found that myeloma cells lacking expression of the interferon regulatory factor 4 (IRF4) gene died, regardless of the underlying genetic mutation. Further experiments to identify targets of IRF4 showed that the MYC gene was a direct target in activated B cells and myelomas, and that IRF4 itself was a target of Myc, creating an autoregulatory loop.

"Our data demonstrate that myelomas are addicted to an abnormal regulatory network controlled by IRF4, irrespective of their molecular subtype and underlying oncogenic abnormalities," Shaffer and colleagues conclude. "Hence, IRF4 emerges as a master regulator of an aberrant and malignancy-specific gene expression program relevant to all molecular subtypes of this cancer."

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