Leukaemia & Lymphoma NI have been supporting research for more than 50 years with the aim of finding the cause and cure of blood cancers.

Leukaemia & Lymphoma NI support some of the infrastructure, students and scientists in the Blood Cancer Research Laboratories in the Centre for Cancer Research and Cell Biology (CCRCB) and Belfast City Hospital.

We support research in the areas of Acute Myeloid Leukaemia (AML) and Myelodysplastic syndromes (MDS), Chronic Myeloid Leukaemia (CML).

To continue with this life saving research we need to raise at least £500k every year. See the links below for more information on our research groups.

View Team

Our Research Team

Our team of researchers who dedicate their time to finding cures and medicines for fighting Leukaemia & Lymphoma.

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Prof Ken Mills

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Prof Mary-Frances McMullin

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Dr Sandra Irvine

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Dr Melanie Percy

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Dr Lisa Crawford

Caroline Crothers, Leukaemia & Lymphoma Co-ordinator

Dr Kyle Matchett

AML/MDS Research

Principal Investigator: Professor Ken Mills

  • The number of molecular abnormalities in Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS) are becoming increasing complex. We now have a better understanding on the types and frequency of mutations that occur in these diseases.

However, both AML and MDS are, in general, a disease of the elderly; the average age at diagnosis is around 63-68 years old. Elderly patients do not respond to therapy as effectively as those younger patients with a similar type of disease. There are number of reasons but a major one is that elderly patients are often less able to tolerate intensive chemotherapy protocols.

Utilising molecular and biological mechanisms of leukaemia, lymphoma and other blood cancers, to develop novel therapeutic approaches

Utilising molecular and biological mechanisms of leukaemia, lymphoma and other blood cancers to develop novel therapeutic approaches.

Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. One of the most important novel therapeutic advances in MM has been the disruption of the ubiquitin proteasome system (UPS) through the use of proteasome inhibitors. Although treatment for MM has considerably improved in the past decade, MM remains incurable and the identification of novel treatment strategies remains a priority. As knowledge of the UPS has increased, it has become evident that there may be other potentially druggable targets within this system which would confer greater specificity, in particular E3 ligases.

This proposal seeks to identify key E3 ligases that contribute to the pathogenesis of MM. In pilot studies we have identified several UPS enzymes that demonstrate abnormal expression across MM cell lines and a small cohort of MM samples. Three of these enzymes are TRIM proteins, a family of E3 ligases that are emerging as important regulators of tumorigenesis. The main aims of this study will be to confirm the expression of these enzymes in MM and to investigate their function in MM. The proposed study may have potential implications for the development of novel therapeutics that could be brought forward for further pre-clinical and clinical evaluation.

Repurposing approved drugs for blood therapies

Current therapies for many of the blood cancers, particularly AML and MDS, are unable to be tolerated by elderly or the more vulnerable patients.    Novel and targeted therapies are also very expensive.   This study will examine the potential of repurposed drugs for blood cancer research.  Repurposed drugs are those that are currently, or have been, used for other cancers or other diseases such as diabetes, dementia or cardiovascular disease. 

Collaborative Drug Development in AML

Genetic and epigenetic lesions, including histone modification, underlie the pathogenesis of acute myeloid leukaemia (AML) and are used as prognostic indicators.  Deregulation of transcription factors is a hallmark of leukaemia however targeting such proteins is difficult. Chemical epigenetic modifiers, that control transcription factor expression, are showing promise in clinical trials.  Histone 3 lysine 4 trimethylation, associated with active gene transcription in haematopoietic stem cells, is tightly regulated by a family of histone methyl transferases (HMTs) and histone demethylases (HDMs).

Golden Anniversary Clinical Research Fellow section

The BCR-ABL1-negative classic myeloproliferative neoplasms (MPN), polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis are clonal stem cell disorders associated with an increased production of mature blood cells belonging preferentially to one cell linage. They share substantial phenotypic mimicry, can undergo phenotypic shifts (from PV to ET and vice versa) as well as evolution to myelofibrosis (post- PV/post-ET myelofibrosis), and may eventually progress to leukaemia.  MPN provide several tractable clinical and laboratory characteristics that allow us to study response to therapy at a clonal level – particularly the ability to grow colonies which contain sufficient numbers of cells for simultaneous genotyping and phenotypic analyses.

The pathogenesis of MPN is associated with mutations that affect cytoplasmic proteins involved in cytokine signaling, either resulting in a gain-of-function (JAK2 and MPL) or a loss-of-function (CBL and LNK).   However, recently, genomic analysis has identified a second group of mutations that affect proteins involved in the epigenetic regulation of transcription, such as TET2, ASXL1 and EZH2. Therapy of these disorders is now focusing initially on inhibition of tyrosine kinases in particular the JAK kinases. The first JAK inhibitor which has been shown to have clinical efficacy in myelofibrosis is Ruxolitinib. This drug has been shown to have some potential in PV and ET but now needs to be fully evaluated. It is proposed to use respectively high-throughput sequencing, transcriptional profiling (at clonal level), epigenetic approaches and signalling studies to characterise patient-specific factors that determine response to therapy. By focusing on samples from patients in a prospective clinical trial and integrating results, genome-wide insights into the patient-specific genetic and epigenetic factors that determine response to treatment can be achieved

This proposal will investigate the relationship between mutation status (group 1: cell signalling genes; group 2 epigenetic associated genes); epigenetic changes; and clinical response in the MAJIC trial.  The two arms of the MAJIC study will enable the student to address, amongst others, questions that include what is the hierarchy of mutations of epigenetic and tyrosine kinase genes in clinical response would the combination of Ruxolitinib and epigenetic therapies are beneficial for refractory MPN patients and in which patients. (The next generations of therapies for MPN are combinations of JAK inhibitors and Histone deacyetylase inhibitors so this information will be crucial for further treatment development).

In the second stage, banked blood and bone marrow samples will be obtained from patients entered into the MAJIC trial prior to commencing treatment with Ruxolitinib and at 1 year (or Complete Response or transformation if sooner).  Mononuclear cells will be isolated from the samples and DNA and RNA (and protein if possible) extracted for further analysis.   An additional sample from buccal cells will have been taken from the patient prior to the trial and could be available if the data suggests that it is needed for this study. 

Chair of Experimental Haematology Grant section

Recurrent development grant to the Professor of Experimental Haematology to support blood cancer research thus enabling short term extensions to contracts for post-docs or graduate students; support for visiting scientists and students; purchase and maintenance of medium scale equipment; attendance at conferences and other events by covering travel, accommodation and registration; and cost of publishing manuscripts.

Lymphoma Clinical Trials

Lymphoma Clinical Trials Fellow

LLNI have provided funding to support a clinical haematologist, who will develop relevant skills in lymphoma treatment and trials through a short term secondment to the University of Southampton

Stem Cell Harvest

Stem Cell Harvest Grant

The research technician supported by this grant undertakes the assessment of stem cell harvests, processing of samples collected through the NI BioBank and other research projects. 

Core Tissue Culture

Recurrent grant to cover the reagents and plastic ware for tissue culture studies across all project of blood cancer research

Financial support for Northern Ireland patients in trials

This grant supported the opening of the AML18 and 19 Clinical trials across Northern Ireland by providing provision for specific drugs to be included in the trail protocol.

Clinical Trials Nurse

Funding a much needed clinical research nurse support to help deliver and develop a portfolio of clinical trials in myeloma, leukaemia and lymphoma, each with their own series of objectives and endpoints.

  • Research Projects

The research group are looking at two aspects of CML. First of all they are studying a novel protein called CCN3 which is involved in the root of the problem, the stem cells. This protein is present in normal cells but absent in CML cells. Adding pure CCN3 protein to CML cells in the laboratory is able to change some of the leukaemia properties back to normal. The group are collaborating with researchers in France, Italy and USA to see how these findings can be translated into improved treatment for patients.

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The proteasome is a special complex structure found inside cells which is responsible for removing damaged proteins. If these damaged proteins are not removed the cell can become cancerous. A new group of drugs has been developed which are called proteasome inhibitors and are proving very successful in patients who have become resistant to conventional treatments. The group have developed specialised tests to examine the structure of the proteasome in cells from patients to decide which of this group of drugs is most appropriate to use. They are also testing new types of these drugs in the laboratory to determine if they are more effective. This work is being carried out in collaboration with Professor Brian Walker of the school of Pharmacy and with research groups in Glasgow, Sheffield and the Dana Faber Institute in Boston.

The proteasome is a special complex structure found inside cells which is responsible for removing damaged proteins. If these damaged proteins are not removed the cell can become cancerous. A new group of drugs has been developed which are called proteasome inhibitors and are proving very successful in patients who have become resistant to conventional treatments. The group have developed specialised tests to examine the structure of the proteasome in cells from patients to decide which of this group of drugs is most appropriate to use. They are also testing new types of these drugs in the laboratory to determine if they are more effective. This work is being carried out in collaboration with Professor Brian Walker of the school of Pharmacy and with research groups in Glasgow, Sheffield and the Dana Faber Institute in Boston.

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Chronic Myeloid Leukaemia Research Team

Post-doctoral scientist:

  • - Dr Lisa Crawford

Post-graduate scientist:

  • - Cliona Johnston

Research Technician:

  • - Anne Jordan

Molecular Basis for Leukaemia Initiation and Maintenance

Principal Investigator: Dr Alex Thompson

  • The molecular landscape of normal and malignant haematopoiesis is being constructed globally by the use of advanced technologies including next generation sequencing (NGS), transcriptomics, epigenomics and proteomics. Such data hold the promise of better diagnosis, prognosis and potentially therapeutic intervention. Translation of these findings to the clinical setting, however, requires the development and application of relevant model systems and determination of druggable molecular pathways. Targeted drugging of the cells and pathways involved in maintenance of the disease is a primary focus of our group.

The Victoria Montgomery Award - Understanding molecular mechanisms involved in AML

Understanding molecular mechanisms involved in acute myeloid leukaemia (AML) - Victoria Montgomery award.

The number of genes mutated in acute myeloid leukaemia (AML) has expanded as a result of next generation sequencing and as a consequence, the complexity of interactions between these mutations in AML has also been identified. One group involves exclusivity between mutations of the transcription factor genes, NPM1, RUNX1, TP53, and CEBPA, whilst a second group includes mutations in FLT3 and other tyrosine kinases, serine–threonine kinases, protein tyrosine phosphatases, and RAS family proteins.  A third set includes genes encoding components of the cohesin complex, other myeloid transcription factors and other epigenetic modifiers.   Members of the cohesin complex were mutated in 5.9% of AML patients, with the gene mutations mutually exclusive and STAG1 (1.8%), STAG2 (1.3%) and SMC3 (1.3%) were most frequently mutated.  Furthermore, cohesin gene mutations were found to significantly co-occur with NPM1, FLT3 or PTPs gene mutations. 

The cohesin complex involves the SMC1A, SMC3, SMC5, RAD21, STAG2 and STAG1 genes which form a ring structure that regulates chromosome segregation during meiosis and mitosis.  Cohesin functions are mediated by other proteins such as CCCTC-binding factor (CTCF) in the control of gene expression.  CTCF prefers hypo-methylated DNA and this relationship is reciprocal, as CTCF can influence the methylation status of distal regulatory regions.  Therefore, cohesin and cohesin-associated proteins contribute to the regulation of gene expression, alongside DNA methylation, chromatin readers, writers and erasers, promoters and enhancers, by acting as DNA insulators. 

The aim of this studentship is to obtain an insight into the functional role of cohesin mutations in myeloid leukaemia.

Summer Studentship Programme

Funding for five summer research studentships in blood cancer research in the Centre for Cancer Research and Cell Biology (CCRCB) at Queen’s University Belfast.

Three year PhD studentship

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders characterized by ineffective haematopoiesis leading to cytopenia and a significant risk of evolution to the more aggressive acute myeloid leukaemia (AML) in which overall 5-year survival is less than 45% which falls to around 15-18% in patients over 60 years old.      

The pathophysiology of MDS and its progression to AML involves cytogenetic, genetic, and epigenetic aberrations.  Genome-wide and targeted analyses from next-generation sequencing have identified novel mutations of prognostic and therapeutic significance.   Recurrent mutations in more than 45 genes are found in over 85% of cases of MDS and AML. These mutations are found in genes regulating DNA methylation, post-translational chromatin modification, transcription regulation, the RNA spliceosome machinery, cohesion complexes, and signal transduction. Mutations in TP53, EZH2, ETV6, RUNX1, SRSF2 and ASXL1 indicate inferior survival. These mutations may also predict responses to HMA and allogeneic HSCT whilst mutations of the NPM1 gene are associated with the more aggressive progression to AML.  Therefore, a better understanding of the molecular consequences of the interactions of these mutations has important implications on treatment response, prognostication, and novel molecular therapeutic targeting.

This project will build on several studies underway in the CCRCB involving SF3B1 mutations (spliceosome complex), STAG2 mutations (cohesion complex), NPM1 mutations (DNA repair) and the DNA Damage Response Deficiency (DDRD) signature that implicate a defective DNA damage response pathways as a common theme in myeloid malignancies which can be manipulated to enhance therapeutic potential in these diseases that have poor outcome in the elderly and for which there is an unmet need for novel therapies.    In addition, these studies may map across other cancer types including breast and ovarian.

The data from our current studies by introducing CRISPR/Cas9 mediated mutations of SF3B1 or STAG2 followed by RNA-seq, ChIP-seq or SILAC analysis has indicated several disrupted DNA repair or RNA processing pathways that have the potential to be therapeutic targets.  Furthermore, initial analysis has suggested that a number of AML and MDS patients have a signature indicating a deficiency in DNA repair.   In addition, NPM1 mutations occur in around 30-40% of AML patients with a normal karyotype and there is evidence from our collaborators of a novel role for NPM1 in DNA repair.

Alison Williamson / LLNI PhD Studentship

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders characterized by ineffective haematopoiesis leading to cytopenia and a significant risk of evolution to the more aggressive acute myeloid leukaemia (AML) in which overall 5-year survival is less than 45% which falls to around 15-18% in patients over 60 years old.     

The pathophysiology of MDS and its progression to AML involves cytogenetic, genetic, and epigenetic aberrations.  Genome-wide and targeted analyses from next-generation sequencing have identified novel mutations of prognostic and therapeutic significance.   Recurrent mutations in more than 45 genes are found in over 85% of cases of MDS and AML. These mutations are found in genes regulating DNA methylation, post-translational chromatin modification, transcription regulation, the RNA spliceosome machinery, cohesion complexes, and signal transduction. Mutations in TP53, EZH2, ETV6, RUNX1, SRSF2 and ASXL1 indicate inferior survival. These mutations may also predict responses to HMA and allogeneic HSCT whilst mutations of the NPM1 gene are associated with the more aggressive progression to AML.  Therefore, a better understanding of the molecular consequences of the interactions of these mutations has important implications on treatment response, prognostication, and novel molecular therapeutic targeting.

This project will build on several studies underway involving SF3B1 mutations (spliceosome complex), STAG2 mutations (cohesion complex), NPM1 mutations (DNA repair) and the DNA Damage Response Deficiency (DDRD) signatures that implicate a defective DNA damage response pathways as a common theme in myeloid malignancies which can be manipulated to enhance therapeutic potential in these diseases that have poor outcome in the elderly and for which there is an unmet need for novel therapies.    In addition, these studies may map across other cancer types including breast and ovarian.   For example the SF3B1 mutation also occurs in approximately 4-5% of breast cancer cases and whilst the loss of STAG2 expression has been reported in colorectal, gastric, breast, non- and prostate carcinoma.

Initial analysis has suggested that a number of AML and MDS patients have a signature indicating a deficiency in DNA repair; and NPM1 mutations occur in around 30-40% of AML patients and there is evidence from our collaborators of a novel role for NPM1 in DNA repair.    Furthermore, our data form CRISPR/Cas9 mediated mutations of SF3B1 or STAG2 followed by RNA-seq, ChIP-seq or SILAC analysis has indicated several disrupted DNA repair or RNA processing pathways that have the potential to be therapeutic targets. 

The proposed project will be a companion and complementary study within the on-going research in the laboratories of both primary (myeloid malignancies) and secondary (DNA repair) supervisors.   The project will combine laboratory studies with bioinformatics analysis for the determination of the role of DNA repair in the development of myeloid malignancies and in particular disease progression evolution.