At the Heart of Genetic Shenanigans

Chronic myeloid leukemia protein RAD52 may be key to overcoming stem cell power

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) There has been lots of really good news about a rare blood cancer. Several new drugs have been approved to treat all stages of chronic myeloid leukemia (CML). There’s also work happening to go after the disease at deeper levels.

Scientists may have discovered a way to contain wayward and chaotic stem cells that can keep CML active. In this animal study, a protein was identified that seems to be at the heart of CML. Blocking this molecule – RAD52 – in mice disabled CML cells so the disease stopped advancing.

These findings could lead to the development of a treatment that could stop the CML altogether.

"Talk to your doctor about new treatments for leukemia."

Senior study author, Tomasz Skorski, MD, PhD, professor of Microbiology and Immunology at Temple University School of Medicine, explained the objective of the study: "We would like to eradicate the leukemia stem cells and cure patients with CML."

A number of medications are now available to treat CML - a blood cancer that’s caused by genetic shenanigans - from initial to advanced stages. But there’s a wild card in this disease, and those are stem cells that tend to eventually outsmart the drugs. The stem cells start combining a whole slew of genetic mistakes which, over time, re-energizes the disease to continue its march.

A "tah-dah" moment came when the researchers found that the RAD52 protein was the key choreographer of these genetic fireworks in the stem cells.

“"We took advantage of the fact that remaining leukemia stem cells accumulate lots of lethal DNA lesions, but they don't die because they can repair them very efficiently. We attacked the DNA repair pathway in a way that is not going to harm normal cells, which have a different repair mechanism than leukemia cells."

So what does this mean for patients? We asked Neil Shah, MD, PhD, who is Associate Professor of Medicine at the University of California, San Francisco.

"It is hoped that the ability to selectively target and eliminate CML stem cells will lead to true disease cure in patients, and enable discontinuation of therapy altogether. Dr. Skoski and colleagues have performed elegant studies of DNA repair pathways and have demonstrated a strong reliance on the activity of RAD52-mediated DNA repair for CML stem cell survival in vitro [test tubes],” said Dr. Shah, who is leader of the Hematopoietic Malignancies Program within the UCSF Helen Diller Family Comprehensive Cancer Center.

He went on to explain in practical terms what these findings mean. “Over the past four years, several investigators have identified various genes as being critical for the survival of CML stem cells in various model systems. The challenge moving forward will be to translate these laboratory discoveries to effective therapies, which can be challenging not only because it can be difficult to develop tolerable drugs that mimic the activity of the tools used in vitro, but also because we have learned that human cancers quite commonly defy expectations based upon laboratory studies," Dr. Shah told dailyRx News.

The researchers reported their findings at the 54th American Society of Hematology Annual Meeting and Exposition. Research is considered preliminary before it is published in a peer-reviewed journal.

Reviewed by: 
Review Date: 
December 21, 2012
Last Updated:
December 22, 2012