Leukemia society supports UW Medical School researcher

The Leukemia Society of America has put its money on a UW Medical School researcher whose studies show promise for understanding genetic abnormalities associated with leukemia.

The society is supporting Emery H. Bresnick, assistant professor of pharmacology, with a highly competitive, five-year $270,000 career development award.

Bresnick is using the award to continue his National Institutes of Health-funded studies examining the way genes are regulated across long distances on chromosomes.

“A common feature of malignancies is high susceptibility to chromosome breakage,” said Bresnick. “This can lead to disruption of normal gene activity, resulting in cancers such as leukemia.”

Chromosome breakage can affect critical regulatory regions of the chromosome that determine whether an associated gene will be turned on or off, he said. Such breakage can move regulators away from where they ordinarily should be on the chromosome.

To understand the process by which chromosome breakage yields unbalanced reproduction of immune cells, the hallmark of leukemia, Bresnick’s team is concentrating on locus control regions (LCRs) of the cell. LCRs normally regulate and prolong activity of genes located long distances away on the chromosome.

“We are using the LCR as a model to derive general principles of long-range regulation across the chomosome,” he said, adding that insights into how LCRs normally function may provide clues to understanding why cells act abnormally due to chromosome breakage.

Better knowledge of LCRs may also help scientists design more effective approaches to gene therapy, said Bresnick.

“A big problem with gene therapy is that once therapeutic DNA is introduced into cells, it doesn’t stay active very long,” he said. With their ability to enhance and prolong gene activity, LCRs may help solve the problem.

Bresnick’s team will also be examining a specific cell-membrane receptor, called Notch, which controls important aspects of development. For example, Notch sends the nucleus signals that regulate blood-cell formation.

“Chromosome breakage can alter the Notch receptor, causing a breakdown of signals passing through the receptor, producing uncontrolled cell growth such as that seen in leukemia,” he said. “By learning more about Notch and this signalling mechanism we hope to develop compounds that can regulate the abnormal formation of leukemia cells.”