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One Gene May Be Key to Myeloma
Date:6/23/2008

icularly vulnerable parts of cancer cells

"It allows you to inactivate one gene at a time in a cancer cell and then ask what happens," Staudt explained. "We looked simultaneously at thousands of different genes . . . and then asked which one prevents the proliferation and survival of cancer cells."

In this study, the screen identified one gene, IRF4, which surfaced no matter what type of multiple myeloma the investigators looked at.

"Basically, every type of myeloma cell for which we have in vitro models is completely dependent on IRF4, such that, when we inhibit it, they die a swift death within a few days in the lab," Staudt said. "This is better than we hoped."

Interestingly, however, the gene is not mutated when cancer is present. "In the vast majority of cases, there was absolutely nothing different between the IRF4 gene in cancer cells compared to any normal cells," Staudt said. "They were completely normal, yet the cells were totally dependent."

Of course, this begged the question, why?

IRF4 turns out to be a transcription factor, meaning it regulates gene expression -- how a gene produces proteins. In this case, IRF4 regulated the expression of about 35 other genes, including MYC, a well-known cancer-causing gene.

"We found that this IRF4 transcription factor was turning on MYC, which itself is a transcription factor that was turning on IRF4. So, you can see that this is a vicious cycle," Staudt explained. "They cycle out of control, and so this is at least part of how it works."

IRF4 is in charge of so many processes, in fact, that the study authors described knocking it out as "death by a thousand cuts."

"If IRF4 is a master regulator of the working of a myeloma cell, this would be a great drug," Staudt said. "We want people to sit up and take notice of IRF4, because it would be effective across the board in all types of myeloma."

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