Integrative genomics and immunobiology in Hairy Cell Leukaemia

Summary Hairy cell leukaemia is a rare and slowly growing cancer of B lymphocytes. While many patients treated with frontline treatment achieve durable remission, as many as 50% of patients will relapse and need further treatment. Why some patients require additional treatment and others have long term remissions remains unknown. We believe that understanding the genetics of the hairy cells and how the immune system responds to them will help answer this question.

Project Details

Hairy cell leukaemia (HCL) is a rare and slowly growing cancer of B lymphocytes. It has unique features and is often defined by the presence of a specific genetic change known as the BRAF V600E mutation. In some rare cases BRAF V600E mutations are not present and different genetic causes have been identified including our recently reported novel observation of an alternative type of BRAF alteration. For those patients with HCL that does not contain the BRAF V600E mutation there is a need to understand the precise genomic drivers of these atypical cases as those discoveries may critically inform personalized targeted treatment strategies.

Patients with HCL are commonly treated with cladribine (chemotherapy) and rituximab (an antibody targeting B cells) and often achieve complete and durable remission, however as many as 50% of patients experience disease relapse, requiring further treatment. Why some patients require recurrent therapy and others have long term remissions is unknown. We believe that understanding the genetics of the hairy cells and how the immune system responds to them may help answer this question. Our initial findings in the analysis of bone marrow samples taken before and after cladribine treatment has shown that patients with durable remissions have greater rates of immune recovery indicating that treatments that enhance immune recovery may allow long term remissions to be achieved. New molecularly-targeted therapies such as BRAF, MEK and BTK inhibitors provide non-chemotherapy options in HCL. The genomic mechanisms of resistance and the immune impact of these novel agents in HCL are largely unknown and may be of value for guiding subsequent therapy decisions.

This study proposes to further define the genomic and immune landscape of HCL as it relates to diagnosis, therapeutic decisions and disease monitoring in patients. Through this study we will develop and consolidate new discoveries via state-of-the-art genomic profiling and cutting edge immune profiling to help inform personalized treatment and optimize health outcomes. Potential scholarship funding may be available for outstanding candidates.