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 can impact on disease progression, DNA damage repair and response to therapies.  

A second theme is the use 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. Using a novel algorithm driven pair-wise combination screen we can identify possible 2 or 3 drug combinations that are at least as effective as conventional chemotherapy, but with less toxicity. One project, MyBLOCk, is using this approach on diagnostic patient samples to determine optimal therapies for individual patients. These laboratory-based studies are complemented with computational analysis to map drug responses to specific hallmarks of cancer. Alongside this we are investigating is their potential components in snake venom toxins that may be of use as a therapy for blood cancers.  

Changes in the epigenome are an important aspect in controlling gene expression and chromatin structures. The role of histone modifications in determining therapeutic responses in MPN and chromatin remodelling in AML are two of the projects we are investigating. 

In terms of international networks, we are associate partners in the IMI2 HARMONY project on Big Data in Blood Cancers and a full partner in the Erasmus Plus Knowledge Exchange Network NEMHESYS on NGS in blood cancers.  

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 leukaemia (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 with collaborative studies with colleagues in WEIMM. 

We are also involved 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. This includes being leaders within the Primary Thrombocythemia-1 (PT-1) trial, the largest randomised trial in this disorder in the world.

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.