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The significance of recurrent translocations involving programmed death ligands in non-Hodgkin lymphomas

David Twa

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Funding source

Canadian Institutes of Health Research (CIHR)
Though our bodies have many mechanisms to guard against uncontrolled cell growth, sometimes these defences are deregulated. If these safeguards fail in white blood cells called lymphocytes, along with other factors, this can cause a cancer known as lymphoma. Lymphomas are the fifth most common cancer in North America and frequently affect many young Canadians. Additionally, treating lymphoma is often challenging; current anti-cancer drugs are not always specific or effective enough at completely killing the tumour cells. This often results in treatment-related complications such as relapse or secondary cancers. Our research aims to characterise two genes to which a more molecular-precise therapeutic can be designed. To do this, we will screen the genetic material from biopsies of over 1,000 past and current lymphoma patients. Using high-resolution/throughput sequencing and fluorescence staining techniques, we will report on the frequency of changes to DNA of the two programmed death ligand genes. Based on the literature and our preliminary research findings, we propose lymphoma cells have many of these ligands on their cell surface as a result of DNA alterations. These ligands are known to significantly deregulate anti-cancer defence mechanisms and therefore, we believe over-expression of these ligands might explain the difficulties in treating certain people with lymphoma. To further characterize programmed death ligand deregulation, we will perform a variety of cell-based and animal model functional experiments to measure protein and RNA expression levels and cell viability. At the end of our project, our findings will contribute to developing a personalised therapeutic against these programmed death ligands which will be suitable for a subgroup of lymphoma patients. We also believe that our research will contribute to more accurate diagnoses of lymphomas and ultimately, that it will globally improve the prognosis for current and newly diagnosed lymphoma patients.

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