Blood Cancer research is focused on developing and applying pre-clinical models of the sub-types of these diseases; this is complemented by active collaborations with the haematology consultants across Northern Ireland.
Myeloid malignancy, is a spectrum of diseases covering Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasms (MPN) and Acute Myeloid Leukaemia (AML), has an unmet need for new effective and less intensive therapies as the survival rates, particularly in the elderly (over 65 years old) are still poor. There are numerous mutations associated with myeloid malignancies and we are investigating how specific mutations (SF3B1, STAG2 and NRAS), can impact on disease progression, DNA damage repair and response to therapies.
A second angle is focused on identifying potential therapeutic agents repurposed from treatments for other diseases including those used for dementia or diabetes; these studies are being undertaken in adult and paediatric AML. One interesting strand is the potential use of snake venom toxins as therapy for myeloid malignancies. We are also assessing the epigenetics status in MPN patients in relation to their response to therapeutic agents.
Multiple Myeloma (MM), a blood cancer arising in plasma cells, is characterised by the synthesis and secretion of large amounts of abnormal immunoglobulin, known as paraprotein. Targeting protein homeostasis through the use of proteasome inhibitors or immunomodulatory drugs has become the backbone of MM therapy, however, acquired resistance remains a major clinical problem.
Our research focuses on understanding how alterations in protein handling pathways, specifically the ubiquitin proteasome pathway, contribute to the pathogenesis of MM and applying this knowledge to identify opportunities for therapeutic intervention.
Lymphoid malignancies have extremely diverse morphologic features. This diversity, to some degree, correlates with the stage of their differentiation and range from the most indolent to the most aggressive human malignancies. Malignancies of lymphoid cell may present as leukemia (primary involvement of bone marrow & blood ) such as acute lymphoblastic leukaemia (ALL) or chronic lymphoid leukaemia (CLL) or as a one of many sub-types of Hodgkin or non-Hodgkin lymphomas which are solid tumours of the immune system. Our research is mostly focused on the diagnostic classification and therapeutic responses of CLL patients.
This is done through projects involving local analysis of B- or T-cell clonality; p53, SF3B1 or NOTCH mutations which feed into international projects such as ERIC (European Research into CLL) consortium and Euroclonality network.
A vital part of the Blood Cancer Group’s activities are the interactions with clinical colleagues with representation on NCRI working groups for AML, MDS and MPN and are engaged in national and international trials for MDS, AML, MPN and CML supported by the Bloodwise Therapy Acceleration Programme (TAP) portfolio within the NI Cancer Trials Centre.
Group members, attend multi-disciplinary team (MDT) meetings, assess quality of bone marrow harvests, have developed assays for AML mutations that have transitioned into the clinical diagnostic laboratories and are developing next-generation sequencing panels to further extend/enhance the diagnostic and prognostic capability for blood cancers across Northern Ireland.