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Translational CML Study of Nilotinib Versus Imatinib: Focus on Adipocyte Toxicity

By: Joseph Fanelli
Posted: Monday, March 4, 2019

In patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML) treated with nilotinib versus imatinib, significant elevations in fasting glucose and serum lipids and an increased incidence of cardiovascular events were reported, according to findings presented in Leukemia. The 5-year safety update of the ENESTnd trial provided further confirmation that nilotinib is associated with impaired glucose and lipid metabolism, concluded Soban Sadiq, MBBS, PhD, of the University of Liverpool, and colleagues.

“We have shown that repeated exposure of nilotinib and imatinib has contrasting effects on adipocyte lipid accumulation, adipogenic mRNA expression, and secretion of adiponectin,” the authors observed. “Although aggressive screening for cardiovascular risk factors and cardiometabolic surveillance in CML patients [have] been suggested to reduce nilotinib-related cardiometabolic events, there is also a need for therapeutic preventive strategies.”

The researchers underwent a translational study using vitro–in vivo models. A chronic in vitro toxicity model was used to investigative the effects of nilotinib and imatinib on adipocytes. Nilotinib and imatinib were used within their therapeutic ranges.

Dr. Sadiq and colleagues found that neither nilotinib nor imatinib reduced cell viability in undifferentiated and differentiating adipocytes at clinically relevant concentrations. Both nilotinib and imatinib (although to a lesser extent the latter) significantly downgraded Glut4 mRNA expression in differentiating adipocytes. Of note, the downregulation of nilotinib may result in reduced glucose uptake in the adipocyte and perhaps lead to insulin resistance in patients with CML.

Disclosure: The study authors reported no conflicts of interest.



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