The results, which appeared in Clinical Cancer Research, a journal of the American Association for Cancer Research, were obtained by scientists in Japan who were researching the persistent problem of CML resistance to imatinib, the premier drug used in treating the disease.
CML comprises some 15 percent of all adult leukemia cases. Up to 5,000 new cases of the disorder are diagnosed annually in the United States. While people of any age may contract CML, it most frequently strikes those over age 50.
Novartis manufactures imatinib and sells it under the brand name Gleevec. When it was approved in 2001, it transformed the treatment of leukemia. Its main drawback is that from 2 percent to 10 percent of patients are resistant to its action (depending on how resistance is defined). Thus, new CML drugs are often trumpeted as able to overcome imatinib resistance. But the key issue is finding which patients will develop resistance.
In the recent study, a team led by Yusuke Ohba, an associate professor at the Hokkaido University Graduate School of Medicine, explored how a fluorescence resonance energy transfer biosensor could measure the activity of leukemia cells, discovering which were imatinib-resistant.
“Using this test,” Ohba said, “we are now able to identify and predict the most suitable treatment option for individual chronic myeloid leukemia patients. This technique is both sensitive and practical to use; it is especially useful for patients who are in relapse, a case in which the clinician’s important decision regarding the next step in treatment must be made quickly and accurately.”
The scientists used laboratory-cultured CML cells to develop tests for protein levels and activity markers. These assays allowed them to spot the imatinib-resistant cells—and even to plot a subsequent strategy for increasing drug doses, combining therapies, or using second-generation inhibitors.
“The most critical issue in dealing with imatinib resistance is what to switch over to,” the professor said. “If the patient is switched to another drug to which they are also resistant, then the treatment will just be a waste of time and detrimental to the patient’s condition.”
A Clinical Cancer Research editorial written by Yingxiao Wang, an assistant professor in the bioengineering department at the University of Illinois at Urbana-Champaign, called the study a “pioneer work.”
“The entire cancer community is talking about personalized medicine, and key to that is knowing when an individual person will have a unique response,” he said. “This project is an important step forward.”
The test is not yet available in the United States.