Patients with chronic myeloid leukemia who received a glitazone along with imatinib remained disease-free for up to five years in a study published in Nature.

Philippe Leboulch, M.D., a professor of medicine and cell biology at the University of Paris, and colleagues temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia.

The researchers note that glitazones are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). They report that activation of PPARγ by the glitazones reduces expression of STAT5 and the downstream targets HIF2α and CITED2, guardians of the quiescence and stemness of CML leukemia stem cells.

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“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.”

Reference

  1. Prost S, Relouzat F, Spentchian M, et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature. 2015. doi:10.1038/nature15248.