Blocking the Blockers

Chronic myeloid leukemia stem cell enzyme may become new target

(RxWiki News) Drugs known as tyrosine kinase inhibitors are currently state-of-the-art treatment for chronic myeloid leukemia (CML). These medicines don't cure the disease, in part because leukemia has a powerful defense system. Recent research suggests there's a way around these defensive linemen.

Leukemia stem cells are now thought to be the players that lead the charge in CML treatment resistance and relapse. And scientists believe they know exactly the right target to block to break through the resistance.

"Continue to take your medications as prescribed."

Researchers, directed by Ravi Bhatia, M.D. from the City of Hope National Medical Center in Duarte, California, have discovered an enzyme - sirtuin 1 (SIRT1) - protects the tenacious stem cells and plays a role in CML and other cancers.

Chronic myeloid leukemia is a cancer involving white blood cells. Tyrosine kinase inhibitors, the first line therapy fo CML, work wonderfully for a while, before the disease sometimes outsmarts them. 

"Tyrosine kinase inhibitors do not eliminate leukemia stem cells, which remain a potential source of cancer recurrence," Dr. Bhatia a news release announcing his work.

In order to achieve a cure, stem cells have to not only be tackled, but put on the permanent disabled list. 

For the current research, Dr. Bhatia worked with WenYong Chen, Ph.D., Ling Li and their colleagues to determine if the SIRT1 enzyme helped CML stem cells to survive and grow.

They found that, indeed, SIRT1 was seen in high levels in CML stem cells. And that blocking the enzyme reduced the growth and survival of CML stem cells. 

Additionally, inhibiting SIRT1 was seen to activate known tumor suppressor p53.

Dr. Chen says that these findings show how and why resistance to CML treatments occurs. . "We suggest that SIRT1 inhibition is an attractive approach to selectively target leukemia stem cells that resist elimination by current treatments."

Atisha Manhas, M.D., an oncologist in Houston, Texas, told dailyRx in an email, "Dr. Bhatia and colleagues' research advances our understanding of the leukemia stem cells that drive CML, and targeting these cells may eventually lead to a cure of the disease." Dr. Manhas was not involved in the current research.

The study was published by Cell Press in the February 14, 2012 issue of the journal Cancer Cell.

This work was supported by the National Institutes of Health, the Samuel Waxman Cancer Research Foundation, the
Leukemia and Lymphoma Society, the V Foundation and the Glasgow Experimental Cancer Medicine Centre (ECMC).

No conflicts of interest were disclosed.