Gene Expression Profiles in CML Non-responders

Chronic myeloid leukaemia (CML) is a haematological malignancy primarily driven by the fusion oncogene BCR-ABL1, resulting in a constitutively expressed tyrosine kinase. CML is treated very effectively by the tyrosine kinase inhibitors (TKIs) resulting in almost undetectable levels of disease. However, some patients show resistance to first line treatment, requiring second and third generation TKIs. Such resistance is due to the presence of tyrosine kinase domain (TKD) mutations, however TKDs do not appear to be present in all patients who do not respond to treatment. The aim of this project is to utilise gene expression arrays to identify transcriptomic profiles associated with resistance to TKIs in the absence of a demonstrable TKD mutation. The presence of such profiles may allow for a more targeted approach to treatment, if non-responders can be identified earlier in the disease management pathway. Being able to predict those that will not respond to first line treatment will allow for better stratification of patients.