Using massively parallel DNA sequencing to identify leukemia stem cell specific expression signatures, predictive of drug treatment response
|Project Leaders||Marco Marra|
|Project Co-Investigators||Richard Moore, Jacquie Schein, Andy Mungall, Wei Zhang|
For all project related inquires contact:Joanne Johnson
CIRM - HALT
Leukemias are cancers of the blood forming cells that afflict both children and adults. Many drugs have been developed to treat leukemias and related diseases. These drugs are often effective when first given, but in many cases of adult leukemia, the disease returns in a form that is not curable, causing disability and eventual death. During the last few years, scientists have discovered that some leukemia cells possess stem cell properties that make them more potent in promoting leukemia growth and resistance to common types of treatment. These are called leukemia stem cells (LSC).
More than in other cancers, scientists also understand the exact molecular changes in the blood forming cells that cause leukemias, but it has been very difficult to translate the scientific results into new and effective treatments. The main difficulty has been the failure of existing drugs to eliminate the small numbers of LSC that persist in patients, despite therapy, and that continue to grow, spread, and invade normal cells. In fact, the models used for drug development in the pharmaceutical industry have not been designed to detect drugs or drug combinations capable of destroying the LSC. Drugs against LSC may already exist, or could be simple to make, but there has not been an easy way to identify these drugs. Recently, physicians and scientists at universities and research institutes have developed tools to isolate and to analyze LSC donated by patients. By studying LSC, the physicians and scientists have identified the molecules that these cells need to survive. The experimental results strongly suggest that it will eventually be possible to destroy LSC with drugs or drug combinations, with minimal damage to most normal cells. The HALT project will translate this new knowledge into practical, effective treatments.
As a member of the genomics/bioinformatics core of the HALT project, the Michael Smith Genome Sciences Centre will examine transcriptomes of LSC from acute and chronic leukemias using massively parallel DNA sequencing. The analysis of transcriptomes, which will be extracted from very low numbers of xenotransplanted pre- and post treatment LSC,will identify expression signatures which will be predictive of LSC drug treatment response.
For all project related inquires please contact us.
Joanne Johnson, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604 675-8000 x 7901