Scientists Eradicate Leukemic Stem Cells by Targeting Cell Survival Proteins

SCIEX mass spectrometry-based solutions lead to leukemia breakthroughs – advancing Precision Medicine

Framingham, MA — SCIEX, a global leader in life science analytical technologies, today announced an exciting application leveraging SCIEX LC-MS instruments and chemistries. An interdisciplinary research team led by Professor Tessa Holyoake from the University of Glasgow and Professor Tony Whetton from the University of Manchester, UK, has uncovered two proteins that are important to the survival of chronic myeloid leukemia (CML) stem cells. The team used this finding to design a new targeted treatment for CML, demonstrating that dual targeting of the transcription factors p53 and c-MYC can eradicate leukemic stem cells (LSCs). The study was recently published in Nature1 and exemplifies a novel precision medicine approach to advance leukemia research.

Currently, Tyrosine Kinase Inhibitors (TKIs) are used as the standard CML treatment, which has substantially improved patient outcomes over previous therapies. However, these drugs do not kill the LSCs that maintain the disease, so TKIs must be taken continuously by the patient, resulting in ever-increasing costs to sustain remissions. This pressing need to develop curative therapies versus ongoing treatments drove the team to apply a systems biology approach to identify key protein networks that perpetuate the CML phenotype.

Using a systems biology approach, combining both transcriptomic and proteomic analyses, was essential to identify those proteins and corresponding regulators which have a defining role in CML LSC survival. Amongst the SCIEX solutions utilized in this study are the SCIEX TripleTOF® 5600+ System which provides both comprehensive qualitative exploration and high-resolution quantitation on a single platform. iTRAQ® reagents are also used in the study, which are novel labeling chemistries specifically designed for simplifying complex protein expression analysis, enabling researchers to identify key peptides with high sensitivity and selectivity. The scientists found a network of 30 proteins that are central to survival of CML cells and regulated by the p53 and c-MYC transcription factors. The study also demonstrated the novel potential therapeutic advantage of selectively targeting these two transcription factors, which highlights the importance of precision medicine approaches, to provide the right drug, to the right patient, at the right time.

"This collaborative study combined proteomics, transcriptomics and systems biology to identify a novel precision medicine-based approach for eradicating leukemic stem cells," states Professor Whetton. "It is another example of the power that precision medicine holds for the future of treatments, cures for disease and healthcare advancements at large."

Prof Tony Whetton is also Director of the recently opened Stoller Biomarker Discovery Centre at the University of Manchester. The multi-million pound Centre focuses on biomedical research including cancer, psoriasis and arthritis, using mass spectrometry-based proteomics solutions from SCIEX. View online Stoller Biomarker Discovery Centre Opening Symposium, which includes leading researcher video presentations.

"At SCIEX, our mission is to enable powerful scientific insights that deliver life-changing answers," states Jean-Paul Mangeolle, President of SCIEX. "This work is an excellent example of how our MS-based proteomics solutions enable our customers to make important discoveries for the future of precision medicine."

Learn more about SCIEX’s life science research solutions utilized by customers in the advancement of precision medicine.

View the abstract or the Nature article (subscription required): Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

References

1 Abraham, S.A., Hopcroft, L.E.M., Carrick, E., Drotar, M.E., Dunn, K., Williamson, A.J.K., Korfi, K., Baquero, P., Park, L.E., Scott, M.T., Pellicano, F., Pierce, A., Copland, M., Nourse, C., Grimmond, S.M., Vetrie, D., Whetton, A.D. and Holyoake, T.L. (2016) ‘Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells’, Nature, 534 (7607): pp. 341–346.