Every year in the UK, around 4000 people are diagnosed with a type of blood cancer called a Myeloproliferative Neoplasm, or MPN. These are slow-growing blood cancers initiated by a gene mutation occurring in a blood stem cell in the bone marrow – the blood-producing factory in the body.
In a pivotal study published in Science Translational Medicine, the Psaila and Mead groups (MRC Weatherall Institute of Molecular Medicine), together with the Rabinovich lab in Argentina, present new insights into how 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.
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, 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."