Jane Engler
The Role of Lineage and Maturity in Determining in-vitro sensitivity to kinase inhibitors in chronic phase CML
Jane Engler
Imatinib mesylate (Glivec, Novartis Pharmaceuticals) is a drug specifically designed to target the protein which is known to cause Chronic Myeloid Leukaemia (CML). Clinical trials conducted on patients with CML have demonstrated that imatinib works very well in this disease, with many patients entering long term remission.
Because imatinib is relatively new its ability to cure patients of their disease is yet to be determined.
While the majority of patients do respond well, there are a group of patients who, for no apparent reason, fail to respond satisfactorily to the treatment.
The laboratory in which I will be undertaking my Honours year has recently demonstrated that using a very specific protein based assay, patient response can be predicted to a level of statistical significance prior to the patient entering therapy. This is an important finding which will lead to a more rational approach to CML therapy with imatinib, particularly in those patients predicted to do poorly. In these patients increased dose or additional therapy may be advantageous in improving disease response.
While it has been shown that response can be predicted, it remains unclear why some patients will fail to do well on this treatment. My Honours project is designed to look specifically at the underlying causes of patient sensitivity with particular emphasis on the types of blood cells present in the patient when they are first diagnosed. I will also look at the contribution of immature (primitive) leukaemic cells to this sensitivity, and at whether the amount of leukaemia specific protein (BCR-ABL) contributes to sub-optimal response. These studies will provide a further vital insight into CML and the nature of patient response to specifically designed targeted therapies.
