South West

South West

Our research in the South West mainly focuses around The University of Southampton, and we are funding a project at the Plymouth Hospitals NHS Trust. 

Research being carried out in Southampton is looking to improve the treatment and outlook of people living with aggressive lymphoma through a personalised medicine approach. We are also supporting numerous CLL projects that include tackling drug resistance, and supporting projects that want to improve the way doctors manage and treat myeloma and MPN.

We also have a Trials Acceleration Programme (TAP) centre based at Southampton General Hospital, which is being led by Professor Andrew Davis. This centre is part of a TAP network that is helping to speed up blood cancer clinical trials so we can deliver new treatments to people with blood cancer in the fastest possible way. You can find out more about our TAP programme and trials here. 

Our work at the University of Plymouth is around mantle cell lymphoma, which aims to revolutionise the way people with this type of lymphoma are managed and treated.

Plymouth Hospitals NHS Trust

Mantle cell lymphoma has a varied outcome - some cases develop slowly and don’t need treatment straight away, and some will be aggressive and need immediate treatment. But at the moment doctors can’t tell the course of disease at the time a person is diagnosed. Because of this, people are usually treated when they are diagnosed. But in Plymouth, people with mantle cell lymphoma have been watched without therapy if they have no symptoms at diagnosis.

Professor Simon Rule is analysing people who didn’t need therapy for at least 2 years and will compare this to those needing immediate treatment.

It means that the type and timing of treatment can be personalised, and people won’t have to endure harsh treatments unnecessarily. 

Improving the diagnosis of people with mantle cell lymphoma

Lead researcher - Professor Simon Rule, Plymouth Hospitals NHS Trust
Lymphoma Low-grade non-Hodgkin lymphoma (NHL)
Cell Bank: Establishing a Biobank and Database as a National Resource for Characterising Indolent and Aggressive forms of Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is an aggressive lymphoma and generally has a poor outcome. However, it is becoming clear that a subgroup of patients have disease that behaves in an indolent way. It is not yet possible to know who these patients are at diagnosis. It is the norm to treat patients with MCL at diagnosis, however for over a decade in Plymouth, patients have been watched without any therapy if they have no symptoms at diagnosis. This practise has proven that around 30% patients do not need immediate treatment with some requiring no treatment for over 10 years.

University of Southampton

Our research in Southampton has a strong focus on CLL, but we are also supporting a clinical trial that is looking for new ways to treat amyloidosis – a rare bone marrow condition that causes a build up of a protein called amyloid. We are also funding an ambitious project that aims to personalise treatment for people with aggressive lymphoma, and have research that aims to improve our understanding of the genetics behind myeloma and MPN so we can improve the way these blood cancers are treated.

Targeted treatments – drugs that target specific pathways that drive cancer - are transforming the way cancer is treated. But not everyone will do well on these drugs, so doctors are searching for ways to select the best treatments to the individual person, an approach called ‘personalised medicine’. Professor Johnson and his team are working with other researchers across the UK to design a test that will enable doctors to individually tailor treatments for people with lymphoma based on the genetic profile of their disease and additional clinical characteristics.

Chronic lymphocytic leukaemia (CLL) affects certain white blood cells called B cells. The exact causes of CLL are unknown, but molecules on the surface of B cells called B-cell receptors are now thought to play a key role. Two of our research projects in Southampton are focussing on the BCR. Dr Francesco Forconi is searching for new genetic markers associated with BCR activity. Because new drugs that block the activity of the receptor are only effective if the BCR is active, understanding this relationship is important, and could help doctors predict who will respond to new BCR-inhibitors. It’s also becoming apparent that CLL cells can find ways to overcome drugs that inhibit the BCR pathway.

Dr Forconi is also directing a CLL biobank, which collects biological samples from people with CLL. Samples from this bank have been used in research projects that are driving the discoveries in CLL.

People with CLL are usually treated with chemotherapy and immunotherapies, such as rituximab. Although this approach works for many people, some become resistant to their treatment. Dr Stephen Beers and his team want to explore the mechanisms of drug resistance to rituximab, and investigate possibilities for reversing it. And Dr Andrew Steele is also interested in ibrutinib resistance, and wants to find out how this happens, and what can be done to overcome this.

Dr Kim Orchard is running a clinical trial called TRALA in a rare condition called AL amyloidosis. This is where the bone marrow makes abnormal plasma cells, which produce a protein called amyloid. Amyloid can build up in body tissues, affecting the way organs work, and can be fatal if left untreated. People with amyloidosis are usually given high dose chemotherapy, followed by a stem cell transplant. Although this approach works well, many people will suffer serious side effects, such as severe infections. The TRALA clinical trial wants to see if targeted radiotherapy has less side effects than standard treatment.

Multiple myeloma is nearly always preceded by the non-cancerous blood cell disorder termed monoclonal gammopathy of undetermined significance (MGUS). But not all people with MGUS will develop myeloma, and the reasons why only some people with MGUS progress to myeloma are poorly understood. Dr Surinder Sahota’s project wants to map the different patterns of gene changes that happen when MGUS changes to myeloma, and how these differ between individuals. This project could help doctors decide what treatments would work best for each individual affected by myeloma.

Based at The Wessex Regional Laboratory Service in Salisbury, Professor Nick Cross is also looking at genetic changes, but in MPN. This project wants to explore how these gene changes vary between people, and what influences this variation. Information gathered from this research will be used to develop new diagnostic and therapeutic strategies for people living with MPN.


Tackling drug resistance in CLL

Lead researcher - Dr Andrew Steele, The University of Southampton
Leukaemia Chronic lymphocytic leukaemia (CLL)
B cell receptor signalling is modified by IL-4 in chronic lymphocytic leukaemia (CLL)
Signals produced by T cells, another type of blood cell, are able to enhance BCR signalling in the laboratory, and can cause resistance to drugs like ibrutinib.  Dr Steele and his team want to understand how this happens, so that they can develop new treatment strategies to tackle drug resistance in CLL.

Overcoming drug resistance in CLL

Lead researcher - Dr Stephen Beers, University of Southampton
Leukaemia Chronic lymphocytic leukaemia (CLL)
Understanding the regulation of antibody therapy by NOTCH1 mutations in CLL

Dr Beers and his team are using samples from people with CLL to discover the underlying mechanisms of rituximab resistance in CLL. They want to investigate possibilities for reversing resistance, which could lead to designing better treatment strategies for people with leukaemia and lymphoma in the future.

Biobanking: helping to improve the lives of people with CLL

Lead researcher - Dr Francesco Forconi, University of Southampton
Leukaemia Chronic lymphocytic leukaemia (CLL)
Cell Bank: Renewal of a non-trial CLL and mature B-cell malignancies tissue bank as a national resource
Dr Forconi is collecting samples from people with CLL in the UK who have not been entered in a clinical trial. The bank complements the Liverpool UK CLL biobank, which collects samples from people entered in a clinical trial. Samples from this bank have already been used to further our understanding of CLL, and to discover new therapies.

Predicting how people with CLL will respond to new BCR inhibitors

Lead researcher - Dr Francesco Forconi, University of Southampton
Leukaemia Chronic lymphocytic leukaemia (CLL)
The influence of altered genetics on B-cell receptor levels and function in CLL
Dr Forconi is defining the genetic alterations that change the activity of the BCR. This research could identify novel genetic markers associated with BCR activity, and possibly predict how people with CLL will respond to new BCR-inhibitors.

Mapping the genetic changes in MPN

Lead researcher - Professor Nick Cross, University of Southampton
Myeloproliferative neoplasms (MPN)
The molecular pathogenesis of atypical chronic myeloproliferative neoplasms and related disorders
Using state-of-the-art genomic technologies, Professor Cross and his team are identifying new genetic changes in MPNs. They will see what impact these genetic changes have within the biology of MPN, and also how this manifests itself clinically. The information will be used to develop new diagnostic and therapeutic strategies for people living with MPN.


Finding genetic changes that lead from MGUS to myeloma

Lead researcher - Dr Surinder Sahota, University of Southampton
Myeloma
Defining MGUS evolution to multiple myeloma at the single cell whole exome level
Cancer arises fundamentally from mutations in genes throughout the tumour genome, and may progress by accruing further somatic mutations. It is now feasible, using next generation DNA sequencing, to be able to map any mutation in functionally relevant genes across the genome. In any specific cancer type, the question remains how mutations differ between individual patients and, importantly between tumour cells in any given patient, termed intraclonal heterogeneity.

TRALA trial

Chief investigator - Dr Kim Orchard, University Hospital Southampton NHS Foundation Trust
A phase I study of targeted radiotherapy alone for stem cell transplant conditioning in systemic AL amyloidosis
Chemotherapy or high dose chemotherapy and a stem cell transplant are usually given to treat amyloidosis. Although this approach is successful, many people suffer side effects from their treatment, such as serious infections and bleeding from the gut. This trial wants to see if targeted radiotherapy given as part of a stem cell transplant is better than high dose chemotherapy, and if this has less side effects.

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