Researchers in Oxford have identified a protein as a key marker for disease progression and a promising therapeutic target for patients with a type of blood cancer.
In a study published in Science Translational Medicine, the team at the University of Oxford’s MRC Molecular Haematology Unit, working with scientists in Argentina and supported by the NIHR Oxford Biomedical Research Centre (BRC), presented new insights into how myeloproliferative neoplasms (MPN) cancer cells create an environment that fuels progression to a more significant cancer known as ‘myelofibrosis’.
The researchers also identified a protein called galectin-1 that can be used as both a predictor of disease progression and a potential target for future cancer therapies.
Every year in the UK, around 4,000 people are diagnosed with MPN, a slow-growing blood cancer initiated by a gene mutation occurring in a blood stem cell in the bone marrow – the blood-producing factory in the body.
In patients whose cancer has progressed to myelofibrosis, scarring (fibrosis) gradually destroys the bone marrow, preventing healthy blood production.
While treatments can reduce symptoms and control blood counts, there is a lack of therapies that reliably prevent progression to advanced MPNs, such as myelofibrosis. A major obstacle to developing such therapies has been an incomplete understanding of how the cells and molecules in the bone marrow interact to drive cancer progression.
Professor Beth Psaila (pictured, left), a senior study author and MPN specialist, said: “In this study, we wanted to understand how two cell types known to be key players in the biology of MPN (stem cells and megakaryocytes) cooperate with the entire ‘orchestra’ of cells in the bone marrow.
“We discovered that two additional cell types (basophils and mast cells) release inflammatory signals, changing the composition and behaviour of bone marrow niche cells to drive cancer progression.”
Professor Adam Mead, a senior study author and MPN specialist, said: “This work nicely demonstrates how focused use of cutting-edge single cell genomics techniques can uncover new biology and potential therapeutic targets, with the ultimate goal of improving outcomes for patients with blood cancer. We are very lucky to work in a scientific environment at the MRC WIMM with access to such terrific infrastructure and technology platforms.”
The international team showed that ‘dialogue’ between cancer and the neighbouring cells caused both the cancer and the niche cells to produce too much galectin-1. This is a sugar-binding protein widely investigated by Professor Gabriel Rabinovich at the Institute of Biology and Experimental Medicine in Buenos Aires, concerning its role in tumour-immune escape.
The researchers showed that levels of galectin-1 strongly predicted MPN progression in several large independent cohorts of patients, and, importantly, that neutralising the galectin-1 prevented cancer progression in model systems.
Professor Rabinovich said: “We have long been interested in the role of sugar-binding proteins like galectin-1 in solid cancers and in immunity, so we were fascinated to hear from the team in Oxford when they discovered a new role for galectin-1 in MPNs – and thrilled when the galectin-1 neutralising antibody that we developed worked so effectively in their model systems.”
Professor Psaila added: “This study is a brilliant example of the power of collaboration in science – both between academic institutions and between discovery researchers and clinicians. We would not have been able to complete this work without the support, resources and expertise of our international friends and colleagues – and the participation of patients who not only donate their samples to research but also help us set our research priorities.”
As well as the Oxford BRC, the research was supported by Blood Cancer UK, the Kay Kendall Leukaemia Fund and CRUK.