You may remember that the Sussex Cancer Fund recently purchased a new Cytoflex Flow Cytometer for one of the Brighton Medical School research teams headed by Professor Chris Pepper and Dr Andrea Pepper.
The aim is to get a better understanding of Chronic Lymphocytic Leukaemia (CLL) and subsequently develop new treatment.
We were delighted to hear that the Cytoflex Flow Cytometer has been put to good use and a research paper reporting the team’s findings has just been accepted for publication.
We caught up with Dr Andrea Pepper to hear more: “Chris and I are very excited to report that our latest research on Chronic Lymphocytic Leukaemia (CLL) has been accepted for publication in the top international journal for Haematology BLOOD. It is a Brighton and Sussex Medical school (BSMS)-driven project, which utilised the expertise of many of our national and international collaborators during in lockdown. The paper contains an extensive amount of novel data and a very large proportion was performed at BSMS on the CytoFLEX flow cytometer that was funded by Sussex Cancer Fund. Without this instrument, we simply would not have been able to do the project as our previous flow cytometer was both unreliable and dated. We remain heavily indebted to the Sussex Cancer Fund for this contribution and for their continued support of our research.
Chronic Lymphocytic Leukaemia (CLL) is a blood cancer affecting cells that help fight infection called B cells. It is the commonest Leukaemia in the western world and patients with CLL have a high risk of dying from infections. The B-cell receptor pathway (BCR) is known to play a major role in the pathology of CLL cells and inhibiting it with drugs such as Ibrutinib has revolutionised treatment of CLL. However, these drugs are not curative and substantial proportion of patients will only partially respond or become refractory. It is therefore clear that there are other signalling pathways that are utilised by CLL cells to help them survive and expand.
Survival and expansion of CLL cells are dependent on their ability to migrate between the peripheral blood and lymph nodes. In this publication we have identified that CLL cells from some patients can signal through a BCR independent pathway, the Toll-like receptor 9 (TLR9) pathway, resulting in increased migration. This is providing them with a mechanism for resistance to drugs such as Ibrutinib. Furthermore, we have demonstrated that CLL patients have increased levels of the TLR9 trigger (unmethylated DNA) in their blood compared with healthy individuals, and those with poor-prognosis have the highest levels. Finally, in laboratory-based experiments, we have shown that dual inhibition of TLR9 and the BCR synergistically inhibits CLL cell migration. Taken together, these data highlight a role for TLR9 in the pathology of CLL and a promising dual-targeting strategy for more effective treatment of this incurable disease.
As a result of the data in this publication, and an additional pilot study, we have also been awarded a 3-year Medical Research Council (MRC) grant to investigate these findings further. The CytoFLEX will be essential for this work. We hope that this project will provide us with a response predictor for current therapies and also identify promising therapeutic strategies for drug-resistant patients”
We are delighted to hear the progress the team is making and look forward to hearing more about their groundbreaking research. If you would like to help the Sussex Cancer Fund support projects like this and others looking to understand cancer better and find new and improved treatments you can donate using the button below.
