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“If cancer stem cells lie at the heart of some cancers, then being able to predict the behavior of tumors and providing effective therapies against them means understanding the abnormal growth pathways within the stem cells themselves.”
- John Dick, Project Leader (UHN)
“The only reason that I'm willing to take a risk on this project is my confidence in the quality and camaraderie of my colleagues.”
- Scott Tanner, Principal Investigator (University of Toronto)
“We're examining DNA not for its well-recognized role as the genetic material to store and transmit genetic information, but rather for its less-known potential to act as a novel cancer diagnostic tool.”
- Yingfu Li, Principal Investigator (McMaster University)
“We're gaining more understanding of cell defects and how to modify them, so that treatment is no longer a shotgun approach, but more like an arrow aimed at a specific target.”
- Mark Minden, Principal Investigator (OCI)
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Dr. Mark Minden's lab at the Ontario Cancer Institute of the University Health Network will have two principal tasks in this Genome Canada project. First, our group will complete gene expression profiling (by microarray analysis) of leukemic stem cells (LSCs) and hematopoetic stem cells (HSCs) in order to identify which genes are differentially expressed between the two cell types. Later in the project, we will provide candidate patient samples to be analyzed using the Stemspec Protocol and assess the data produced by the method in order to determine the prognostic and diagnostic significance of the proteomic signature of the LSCs.
Microarray analysis is a method for concurrently analyzing the expression of thousands of genes from a population of cells. This method allows scientists to compare between classes of cells (like HSCs and LSCs) and determine which genes have been turned on, off, up or down.
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The Stemspec Protocol is a key deliverable for this Genome Canada project. Samples from patients will be labeled with element-tagged affinity products, analyzed with the new ICP-MS instrument (designed for discrete particle assay), and compared to our database of biomarker fingerprints. The data generated by this method will be used to determine if LSCs are present, and what type of leukemia they represent.
Since LSCs are responsible for maintaining leukemic disease, it is reasonable to assume that specific properties of the LSC determine the diagnosis and prognosis of a patient. If we can define a set of biomarkers that uniquely identify LSCs and subtypes of LSC, those biomarkers (and affinity products that bind to them) can presumably be used to distinguish between LSCs and the other cell types in a patient sample.
Our lab will be responsible for analyzing the gene expression in the leukemic and hematopoietic stem cells provided by Dr. Dick's lab, in order to identify genes whose expression differs between the two cell types. The proteins that are expressed from those genes will be used as targets for affinity product development.
Later in the project, we will select specimens from the Ontario Cancer Institute cell bank for analysis using the project's suite of affinity reagents and the ICP-MS instrument. We will choose archival samples from leukemia patients with known good or poor outcomes to be compared by the Stemspec method. We will then analyze the information that is generated from the assay to determine whether the data collected using the selected biomarkers is sufficient to identify LSCs in patient samples.
Next, we will determine whether the suite of affinity products, in combination with the instrumental analysis, provides sufficient data to allow us to distinguish between the ICP-MS "fingerprints" of patients with good and poor leukemia outcomes.
The ability to find the leukemic stem cells in a patient sample, and to rapidly determine the specific characteristics of that patient's LSCs, will be a valuable step towards providing patients with treatment that is specific to their disease.
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