Leukemia Cells Exploit DNA, Cause Disease

A recent study discusses the discovery of a leukemia-specificed stretch of DNA known as an enhancer element that works to enable cancerous blood cells that proliferate in Acute Myeloid Leukemia (AML), a devastating type of cancer that is roughly incurable in 70 percent of patients. Researchers note that the results provide a mechanistic insight into a potentially new class of promising drugs. 

Researchers discovered an enhancer element that works to control the MYC ongogent specifically involved in leukemia cells, and unlike many other DNA-based gene regulators, the string of DNA "letters" is not near the Myc gene that helps regular the cells. 

"The enhancer elements we discovered are 1.7 million DNA bases away from their target gene, Myc," Vakoc said, via a press release. "But we were able to show that this long stretch of the genome is bent and looped in the cell nucleus in such a way that the remote enhancer segment literally touches the distant segment harboring the cancer gene. Our results suggest that this regulatory conformation fuels the uncontrolled growth of cancer cells and may explain why the Myc gene is so uniquely sensitive to targeting with a new class of drugs being developed for leukemia." The Vakoc lab in 2011 discovered a novel therapeutic strategy to shut off Myc in cancer, an approach now being tested in phase 1 clinical trials.

The researchers identified the SWI/SNF protein complex via an experiment that examined the protems that stop AML disease progression while still allowing healthy cells to normally grow. They also worked to determine if the genome SWI/SNY attaches to DNA. 

"We usually look for duplicated genes in cancer," Vakoc says. "But this is the first time we've ever seen DNA for an enhancer, rather than for a gene, being a common duplication in a cancer type."

"This happens only in leukemia, meaning the enhancer is unique. The work thus identifies an important mechanism that enables leukemia to proliferate. This in turn explains how leukemia drugs that have recently been discovered exert their beneficial effect. One notable example is a drug called JQ1 that Vakoc identified in 2011 as an inhibitor of a cancer-promoting protein called Brd4, which plays a pivotal role in the AML disease process. JQ1 likely blocks the interaction between Brd4 and the same enhancer element identified in the newly published research. This then sets off changes in the cell nucleus that prevent Myc expression."

More information regarding the study can be found via the journal Genes & Development.