
More than 6,600 cases are expected to be diagnosed in the United States this year, and about 1,140 people will die from the condition, according to the American Cancer Society. Seen mostly in adults, chronic myeloid leukemia tends to be slow-growing, but can transform into a rapidly growing form that can quickly kill. Together with his team, study author Dr. Philippe Leboulch, a professor of medicine and cell biology at the University of Paris, temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia. Both drugs are available in pill form.
Pioglitazone is marketed as Actos. Although imatinib and other so-called tyrosine kinase inhibitors have significantly improved outcomes for this type of blood cancer, leukemia stem cells can develop a resistance to this standard treatment because of the dormant malignant cells in bone marrow. In the study -- published online Sept. 2 in the journal Nature -- Leboulch described the molecular pathway leading to "quiescence," or cell dormancy, in chronic myeloid leukemia. The study suggested that glitazones can block this pathway, and, when used with imatinib, render patients disease-free for months to years after glitazones are discontinued. It's unclear how the dormant, drug-resistant leukemia cells were killed using this combination therapy. But an editorial accompanying the study said the cells are "probably either killed directly or driven to exit quiescence, which may lead to their eradication by [imatinib]." Dr.
Jeffrey Schriber, a hematologist with Arizona Oncology in Scottsdale, said larger trials of this combination treatment are in progress and should yield results within the next three to five years. But since drugs such as imatinib already enable 94 percent of chronic myeloid leukemia patients to remain alive five years after diagnosis -- with only 2 percent dying of the disease in that time -- adding in glitazones is "unlikely to make a significant difference" compared to current results, he said. "From a scientific standpoint, however, the principles are critical and go beyond the therapy of CML," added Schriber, who specializes in the field of stem cell transplantation. "This principle could also be potentially applied to other leukemias where the results are not nearly as promising," he said. The major weakness in the new study is its small size, Schriber said, making it difficult to know if the results would hold up in a larger group. Greenberger said it would be ideal to run a randomized controlled trial directly comparing the effectiveness of combination therapy (imatinib and a glitazone) versus imatinib alone.
Patients can take glitazones for months without serious side effects, Greenberger said. "It would be best to see over years if [the combination therapy] could molecularly remove this disease," he said. More information The U.S. National Cancer Institute offers more about chronic myeloid leukemia.

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