July 20, 2013 | by Denise Heady
Chronic myelogenous leukemia (CML) can be difficult to treat, even with today’s powerful modern medicine.
Drugs can inhibit the disease’s signature damaging protein, BCR-ABL kinase, and they can be effective in eliminating mature leukemia cells. But they also can fail to eliminate leukemia stem cells. These stem cells can hide away in the bone marrow and re-emerge after treatment, leading to recurrence.
Ravi Bhatia, M.D., director of the Division of Hematopoietic Stem Cell and Leukemia Research at City of Hope, is researching new ways to target the leukemia stem cells in CML – and his work is gaining increasing attention.
The Samuel Waxman Cancer Research Foundation recently awarded Bhatia a $100,000 grant to further his research. The foundation, dedicated to curing and preventing cancer, is especially interested in differentiation therapy, or the reprogramming of cancer cells. It has funded the work of more than 200 researchers across the globe and has supported Bhatia with $200,000 in grants already.
Bhatia, who studies the fundamental processes of gene regulation and cell survival, already has found that the enzyme SIRT1 contributes to growth and drug resistance of CML stem cells. Conversely, he’s found, inhibition of SIRT1 reduces growth and survival of CML stem cells. Further, SIRT1 inhibition activates the p53 gene, which is an important tumor suppressor.
"These results are significant because they indicate that agents that inhibit SIRT1 and activate p53 can selectively target leukemia stem cells, enhancing the possibility of a cure for CML patients," Bhatia said.
Bhatia is also collaborating with other Waxman Foundation grantees, studying additional gene targets, including EVI1 and NF-kB that could be inhibited to potentially enhance elimination of CML stem cells.