You are here
Cell marker found for leukemia-initiating capacity in chronic myelogenous leukemia
University of Alabama at Birmingham researchers have found a marker on blood cells that may help the most pressing problem in chronic myelogenous leukemia, or CML, today — an inability to get patients off treatment.
“To do that, we have to be able to maintain their remission after stopping treatment,” said Ravi Bhatia, M.D., division director of hematology and oncology in the UAB Department of Medicine, and deputy director of the UAB Comprehensive Cancer Center. “Treatment using drugs called tyrosine kinase inhibitors, or TKIs, do not eliminate leukemia-initiating cells.”
In most patients, residual leukemia-initiating cells result in regeneration of leukemia, necessitating lifelong treatment with these drugs. Only a small proportion of CML patients stay in remission after stopping TKI treatment. Two keys to containing remission may be the ability to identify those patients who will be able to successfully stop their TKI, without later relapse and, second, the ability to identify patients who may benefit from an additional drug regimen besides TKI to achieve treatment-free remission.
Research by Bhatia and colleagues, published Feb. 15 in The Journal of Clinical Investigation, shows that the leukemia-initiating stem cells in the bone marrow are not uniform. Instead, evidence points to a mixed, or heterogonous, population of cells that can be distinguished by several cell markers, significantly Mpl gene expression. Cells with high Mpl gene expression are prone to initiating the disease-causing profusion of white blood cells when tested in a mouse model of chronic myelogenous leukemia, or CML.
The low Mpl gene expression group engrafts in the bone marrow without producing disease. Thus, among the long-term hematopoietic stem cells (LTHSC) found in CML, the Mpl marker distinguishes a group that appears to be leukemic and a group that appears to be non-leukemic. Similar cell-marker differences were seen for LTHSC studied from human CML patients. These findings imply that, among CML LTHSC, it is the leukemic LTHSC that will cause disease relapse if TKI therapy is stopped.
“This shows that not all leukemia stem cells are equal,” Bhatia said. “Some are more prone to causing leukemia and relapses, while some others may just hang around without potential for contributing to relapse.”
Over the past 15 years, chronic myelogenous leukemia has had a marked improvement in five-year survival, from about 30 percent to nearly 90 percent today. This improvement comes from TKI drugs. However, the drugs have to be taken every day for a patient’s lifetime, and their yearly cost can be $100,000 to $150,000. This is a societal burden, and for some patients the drug co-payments can exceed their ability to pay. Identifying patients who could safely stop TKI treatment would be a boon.
Full article here:
- Google Plus One
- Share on Facebook
- Log in or register to post comments
- Email this page