Blood cancers are complex but we are confident that we can continue to improve the recovery rate. Support in this region for NEPAC has in the past made progress possible. With your support, we can help even more patients and their families. Our progress here in the North will then also provide insights to help others around the world. Stephen Proctor, Professor of Haematological Oncology, Newcastle University
Professor Stephen Proctor
The NEPAC Charitable Trust gives most of its money to support blood cancer research, particularly into non-Hodgkin’s Lymphoma. In the last 25 years, the charity has been a major contributor to the success of lymphoma research in the Newcastle University Medical School and the RVI, Newcastle, led by Professor Stephen Proctor.
During this time, the research team has made considerable progress in the management of Hodgkin Lymphoma in adolescents and adults, and recovery rates for teenagers in this region are the best seen in the UK. In the more common lymphoma, non-Hodgkin’s Lymphoma, again there have been major improvements. Much remains to be done however to improve recovery rates for the elderly, where cure rates remain poor.
The team in Newcastle is able to draw on the largest lymphoma database in the world to improve predictions of which treatments are most likely to succeed with individual patients. Professor Proctor retired in 2010 after building up one of the top research units into blood-related cancers in Europe and leaving patients in the North East benefiting from world-class innovations in blood cancer treatment.
Since Professor Proctor’s retirement, NEPAC has continued to support lymphoma research in the Newcastle University Medical School and, to date, five researchers have received our support starting with Dr Venetia Bigley in 2011.
Support for Dr Venetia Bigley
By 2010, there were sufficient funds in the George Walker Appeal to half fund a Fellowship in George’s memory. Dr Venetia Bigley was appointed George Walker Clinical Fellow in the Institute of Cellular Medicine at the University and took up the four year post in January 2011. Venetia graduated in Natural Sciences at Cambridge before converting to medicine at UCL. After clinical work in various London hospitals, she moved to Newcastle in 2004 to pursue her training in haematology and complete a PhD.
Her primary clinical interest is in bone marrow transplant and its use in the treatment of lymphoma, as increasing numbers of patients now receive a bone marrow transplant to treat lymphoma. This is the only potential cure for low grade non-Hodgkin’s Lymphoma. In the research field, she is particularly interested in the immune system in blood-related diseases and specifically a type of cell called a dendritic cell which plays a key role in a healthy immune system and is believed to be involved both in the development of blood cancers and potentially in their cure. These cells also have a close link with another immune cell, the B-cell, which is the malignant cell in lymphoma. She is extending these recently developed techniques to lymphoma research to better understand how the immune system is altered in lymphoma, why bone marrow transplant treatment is proving so successful and how to further improve outcomes.
A major discovery has been the faulty gene in a new hereditary disease affecting the immune system in young adults. This condition, called DCML deficiency, causes a predisposition to infections and blood cancers including, in a few cases, lymphoma. This discovery is helping to better understand how the development of normal immune cells, including B cells (the cells that turn cancerous in lymphoma), is controlled. It also allows the diagnosis of a previously unrecognised disease and provide genetic counselling and treatment for affected people and their families.
Venetia’s research has made significant progress identifying what controls the formation of B cells at a genetic level and she has identified two novel genes - GATA2, which is critical to B cell development and SHP-1 also important in the development of B cells. When the SHP-1 gene is not working, only very low numbers of B cells are found in the blood and almost none are found in immune organs, such as the spleen, where they would normally react to any infection. Abnormalities of the SHP-1 gene have been found in non-Hodgkin’s Lymphoma. This is helping to understand why lymphoma develops and how to treat it.
This research has been facilitated by the use of a new technology called ‘NanoString’, available in Newcastle since 2014. This allows researchers to gain detailed information about how the genes in cells are behaving to allow a better understanding of what has gone wrong in lymphomas. For the first time, this information can be generated, using the NanoString instrument, from small numbers of cells, such as biopsy samples, and material stored in biobanks can be included.
In June 2013, Venetia was awarded a prestigious Wellcome Trust Intermediate Clinical Fellowship and our support was no longer needed. This internationally competitive award recognises the quality and potential of her research and the excellence of the laboratory, university and hospitals in Newcastle. It is in part due to our funding that she was in a position to successfully apply for this award. Venetia has expressed her sincere thanks for our support and will continue to acknowledge and publicise this in work presented at international meetings and published in journals.
Her ground-breaking research continues and, on the clinical front, she contributes as a Consultant to the care of lymphoma patients at the Freeman Hospital, Newcastle and is the lead physician for the care of patients with non-Hodgkin’s Lymphoma who are about to have, or have had, a bone marrow transplant.
Support for Dr Rachel Crossland
The NEPAC Trust also supports blood cancer research within Northern Institute for Cancer Research within the Newcastle University Medical School.
Research being undertaken by Dr Rachel Crossland and Dr Tryfonia Mainou-Fowler (now retired and a Trustee of NEPAC Trust) focusses on the identification of markers that can more accurately identify those patients at diagnosis that are likely to develop a particularly aggressive lymphoma. The biological function of these markers can then be investigated in more detail, in order to help further understand the biology of the disease and identify targets for the development of new, improved treatments. There are many different types of non-Hodgkin’s Lymphoma. Some lymphomas are slow-growing and are usually controllable but not curable. Others are more aggressive, but may be curable with very intensive treatments. Early diagnosis and prognosis is important in ensuring that patients receive the best care. There are some systems to help the clinician predict for outcome at the onset of the disease but these are based on clinical factors and are not always correct. NEPAC support has allowed these researchers to gain a better understanding of the biology of the disease and the factors involved, in the hope that this will help to develop better prognostic systems and improve treatments. Specific biological markers that are expressed by the cancer cells of the aggressive type non-Hodgkin’s Lymphoma have been identified. These markers predict for outcome and improve upon a prognosis based on clinical systems alone.
Following Dr Mainou-Fowler’s retirement, Rachel continues her lymphoma research alongside Dr Vikki Rand, Bloodwise Senior Bennett Fellow in the Wolfson Childhood Cancer Research Centre at the University. Dr Rand has a strong background in genetics and the current project is planning to use some of the most recent advances in genetic sequencing to screen particularly aggressive cases of lymphoma for novel mutation patterns in the genes. This should lead to a better diagnosis of these cases as well as an understanding of how their biology makes them less responsive to the currently used treatments. This work is being undertaken in collaboration with the Harvard Medical School.
Another line of their research is investigating childhood lymphomas in both UK and African children. The work focusses on defining sub-groups of patients who do not respond to treatment, or who do initially respond and then relapse with an additional lymphoma. The difference in the genes of these patients is then investigated in the hope that this will allow new and more personalised treatments to be developed. This is being carried out using the new NanoString instrument, which is ideally suited to analysing B-cell tissue samples and provides accurate and extensive genetic information about the sample. Analysis of the results will show what is genetically different about the patients who relapse compared to those who reach complete remission. Exciting results are being achieved and in May 2016, Rachel was awarded a prestigious Affymetrix Tumour Profiling grant in order to expand this work.
Support for Dr Chris Carey
Since October 2015, NEPAC Trust has been funding a post-doctoral research fellow, Dr Chris Carey. After graduating and completing postgraduate medical and haematological training in Newcastle, Chris spent 3 years undertaking lymphoma research at Harvard University, USA. He returned to the UK in June 2015. Keen to practice in Newcastle, Chris was appointed to join the Lymphoma Research Group and he brings with him many new ideas. Our support is enabling him to establish his research here and, in due course, to make application for senior fellowship posts to continue his salary and support. His research aims to improve the accuracy of diagnosis of non-Hodgkin Lymphomas, particularly higher risk subtypes, in the hope that this will ultimately lead to the selection of specific, novel treatments that target each individual patient’s disease. Contemporary scientific research is being adapted and validated for clinical use to provide meaningful benefits to patient care.
Support for Alexander Newman
NEPAC Trust agreed to fund a 3 year postgraduate PhD studentship as from October 2015, under the supervision of Dr Vikki Rand. Medical Sciences graduate, Alexander Newman, took up the studentship and it is hoped that this will help a keen, young researcher to gain valuable experience and enhance future career opportunities. His project specifically studies relapsed non-Hodgkin’s Lymphomas and uses cutting-edge techniques to investigate the genomes of non-Hodgkin’s Lymphoma patients. Comparing the genomic abnormalities in patients who respond to treatment with those that do not should lead to an understanding of the underlying causes of resistance to current treatments.
Support for Masood Zaka
NEPAC Trust is also funding a Post-Doctoral Research Assistant and
Masood Zaka was appointed to this two year post, as from 1st August 2017. Masood has degrees and experience in bioinformatics and brings a lot of computational data analysis skills to the group. He has already produced some exciting results from Dr Crossland's data and will help others in the group with data analysis.
It is rewarding that the Lymphoma Research Group continues to grow in Newcastle due, in part, to the consistent financial support of the NEPAC Trust through the George Walker Appeal. A big thank you to all our supporters and donators - their contributions really make a difference to lymphoma research in the region. North East patients benefit first from this research followed by the rest of the world.
Looking round the labs, Rosalynde Walker and
Ian Newton of NEPAC, with
Dr Vikki Rand and Alexander Newman.