The Role of KIR3DL2 in T Cell Cancers

Leukaemias and lymphomas, cancers of white blood cells, are divided into categories depending on the type of cell involved, maturation level, and other clinical and genetic markers. Improving our ability to distinguish types and subtypes of T cell cancers, which may have a different clinical course or response to treatment, remains an important goal.
This project will investigate the expression of KIR3DL2 on T cells cancers. This receptor has been described in one form of cutaneous T cell lymphoma, known as Sezary Syndrome, but the aim is to identify any additional types where this protein is present. To this end, a wide variety of cancer samples will be examined for evidence that the KIR3DL2 gene is turned on, or the protein is present. This will be done using RT-PCR, Western blotting and immunohistochemistry techniques. Clinical information will be used to identify any particular group (e.g. late stage or aggressive disease) where KIR3DL2 is commonly found. An additional aim is to understand how KIR3DL2 impacts the cancer cell by examining the types of intracellular signals that occur. This work will first utilise immortalised cell line models which can be easily manipulated and probed. The impact of various characteristics of the receptor including any differences between two common receptor variants found in different individuals will be explored. The impact of KIR3DL2 on a key signalling pathway, and how it impacts on growth and survival signals in the malignant cells will then be examined. Elucidation of the expression profile of KIR3DL2 in different T cell cancers will aid correct classification, diagnosis, and monitoring of disease progression, while understanding of the intracellular effects of KIR3DL2 will provide mechanistic insight into its role in malignant T cells and open up new avenues for therapy.