Gene Silencing Pinpoints Treatment Target for Multiple Myeloma

Cancer researchers studying multiple myeloma have used RNA-interference-based genetic screening technology to identify a possible therapeutic target for this currently untreatable disease.

Investigators at the [U.S.] National Cancer Institute (Bethesda, MD, USA) developed a short hairpin RNA system that effectively allowed them to turn off genes one at a time in order to evaluate the role of each gene on the cell's survival and proliferation.

In a study published in the June 22, 2008, online edition of the journal Nature, the investigators used this system to study 10 laboratory models of multiple myeloma, each representing distinct genetic subtypes of the cancer. They found that a single transcription factor, interferon regulatory factor 4 (IRF4), was required for survival of multiple myeloma cells. RNAi quenching of the gene for production of IRF4 was toxic to all the myeloma cell lines.

Of particular interest was the interaction of IRF4 with the MYC oncogene, which is known to play a significant role in multiple myeloma and other cancers. The study revealed that IRF4 and MYC formed a feedback loop: IRF4 activated MYC, and MYC, in turn, activated IRF4 and - by extension - itself and the myeloma-fueling gene networks that rely on IRF4.

"These findings reveal a hitherto unknown and, for myeloma cells, critical network of gene activity centered on this one protein,” said senior author Dr. Louis M. Staudt, deputy chief of the metabolism branch at the National Cancer Institute. "What we have now is a new window of opportunity for therapeutic development in multiple myeloma.”


Related Links:
National Cancer Institute