Adding Pioglitazone to Imatinib May Improve Treatment of Chronic Myeloid Leukemia
the ONA take:
Patients with chronic myeloid leukemia (CML) who received imatinib plus pioglitazone, a drug commonly used to treat type 2 diabetes, achieved a sustained complete molecular response for up to 4.7 years after the withdrawal of the antidiabetes medication, a recent study published online in the journal Nature has shown.
For the study, Philippe Leboulch, MD, PhD, from Brigham & Women’s Hospital and Harvard Medical School Genetics Division in Boston, Massachusetts, and colleagues temporarily treated three patients with CML in chronic residual disease despite continuous treatment with imatinib with pioglitazone. When pioglitazone activates PPARγ, the expression of STAT5, HIF2α and CITED2 is decreased. These downstream signaling targets play a role in the CML leukemia stem cells that tyrosine kinase inhibitors such as imatinib may fail to eradicate.
"When pioglitazone was given temporarily to three chronic myeloid leukemia patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained complete molecular response, up to 4.7 years after withdrawal of pioglitazone," the authors write.
"This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."
Imatinib is already approved by the US Food and Drug Administration (FDA) for the treatment of adult and pediatric patients with newly diagnosed Philadelphia chromosome positive CML in chronic phase, as well as those in blast phase, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
Erosion of the chronic myeloid leukaemia stem cell pool by PPAR[ggr] agonists : Nature : Nature Publ
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