Seahorse Bioscience XF technology yields insights on leukaemia stem cell metabolism
Seahorse Bioscience, the world leader in instruments and assay kits for measuring cell metabolism, has announced a new milestone: the 500th journal reference including XF assay data. The paper, titled BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells, will be published in the March 7, 2013 issue of the journal Cell Stem Cell.
"Our work demonstrates that there are fundamental differences between the metabolism of leukemia stem cells compared to the mass of tumor and normal cells. We believe our findings have implications for a greater understanding of leukemia stem cell biology and - from a therapeutic perspective - for providing a basis that targeting leukemia stem cell metabolism holds premise as a unique and selective therapeutic approach," stated lead author, Dr Eleni Lagadinou MD, PhD., post-doctoral fellow in the lab of Craig Jordan, the Philip and Marilyn Wehrheim Professor at the James P Wilmot Cancer Centre at the University of Rochester Medical Center (URMC) in Rochester New York.
Dr Lagadinou and the URMC team are developing a new therapeutic strategy for acute myeloid leukemia (AML), a highly drug-resistant cancer. They have discovered that therapy-resistant AML cells are a subpopulation of cancer stem cells with a distinctively low energy metabolism. Unlike normal cells, this lethal subpopulation has impaired ability to utilize glycolysis to meet increased energy demands, and is critically dependent on mitochondrial respiration for energy and survival. These findings suggest it is feasible to eradicate therapy-resistant leukemic stem cell populations, by targeting their unique energy metabolism profile with inhibitors of oxidative phosphorylation, such as the BCL-2 inhibitor drugs currently in development with a number of drug companies.
"The XF Analyzer was designed to provide bioenergetic insight into metabolic diseases. We suspected that its ability to measure, in real-time, the changes in cellular glycolysis and mitochondrial respiration would be equally important to cancer research, and this paper proves it,” stated David Ferrick, CSO of Seahorse Bioscience. “Using the XF Analyzer, these scientists were able to unequivocally demonstrate the reliance of leukaemia stem cells on mitochondrial respiration, with a concomitant impairment in glycolytic capacity. Most metabolic research into cancer stems cells has focused on the disproportionate use of glycolysis to fuel the tumor’s extreme energy needs, whereas URMC has demonstrated such a strategy is likely to be unproductive."
Leukaemia is a blood cancer with four common types: acute myelogenous leukaemia (AML), acute lymphoblastic (ALL), chronic myeloid leukaemia (CML), and chronic lymphoblastic (CLL). AML is most common in adults and the most difficult to treat, in part because it affects immature cells. Nearly 50,000 new cases are diagnosed each year, with about half resulting in death.
Seahorse Bioscience XFe Analyzers and stress test kits are the industry standard for the measurement of the metabolic pathways, such as mitochondrial respiration [oxidative phosphorylation] and glycolysis. Scientists worldwide are advancing their research in understanding the role of cell metabolism in neurodegeneration, ageing, cancer, cardiovascular, cell physiology, toxicology & hepatobiology, immunology, infectious diseases, mitochondrial diseases, model organisms, obesity, diabetes, metabolic disorders, screening, and translational medicine.
The University of Rochester Medical Center forms the centerpiece of the University's health research, teaching, patient care, and community outreach missions.