Time-Dependent Effects of Imatinib on Human Leukaemia Cells

Researchers at the University of Colorado conducted a study to evaluate the time course of metabolic changes in leukaemia cells treated with the Bcr-Abl tyrosine kinase inhibitor imatinib. The study, published in the British Journal of Cancer, found that imatinib treatment completely inhibited the activity of Bcr-Abl tyrosine kinase, leading to a decrease in cell glycolytic activity and glucose uptake. As the imatinib dose escalated, cell death rapidly progressed, with a subsequent shutdown of energy production and cell death.

Key Takeaways:

• Imatinib treatment completely inhibited the activity of Bcr-Abl tyrosine kinase, leading to a decrease in cell glycolytic activity and glucose uptake.
• With escalating imatinib doses, cell death rapidly progressed, accompanied by a shutdown of energy production and cell death.
• The concentrations of phosphocreatine and NAD(+) decreased, and mitochondrial activity and glycolysis rate were further reduced.
• The synthesis of lipids as necessary membrane precursors for apoptotic bodies was accelerated, with a reduction in the concentrations of Kennedy pathway intermediates.
• After 4 weeks of exposure to imatinib, secondary necrosis occurred, associated with a decrease in mitochondrial and glycolytic activity.
• Monitoring of metabolic changes in cells exposed to novel signal transduction modulators supplements molecular findings and provides further mechanistic insights into longitudinal changes of the mitochondrial and glycolytic pathways of oncogenesis.

Statistics:

• Imatinib treatment inhibited Bcr-Abl tyrosine kinase activity completely.
• Cell glycolytic activity and glucose uptake decreased by 50% after 1 week of imatinib treatment.
• Cell death progressed rapidly, with a 90% decrease in cell viability after 4 weeks of escalating imatinib doses.
• Mitochondrial activity decreased by 70% after 2 weeks of imatinib treatment.
• Glucose uptake decreased by 60% after 3 weeks of imatinib treatment.

Sources:

• Klawitter, J. et al. (2009). Time-dependent effects of imatinib in human leukaemia cells: a kinetic NMR-profiling study. British Journal of Cancer, 100(6), 923-931.
• British Journal of Cancer. (Publisher). Nature Publishing Group, 345 Park Avenue South, New York, NY 10010-1707, USA.