Unraveling tumor growth one stem cell at a time

Researchers at the University of Cambridge have discovered that a single mutation in a leukemia-associated gene reduces the ability of blood stem cells to make more blood stem cells, but leaves their progeny daughter cells unaffected. Their findings have relevance to all cancers that are suspected to have a stem cell origin as they advance our understanding of how single stem cells are subverted to cause tumors. Published this week in PLOS Biology , the study by Professor Tony Green and his team at the Cambridge Institute for Medical Research (CIMR) is the first to isolate highly purified single stem cells and study their individual responses to a mutation that can predispose individuals to a human malignancy. This mutation is in a gene called JAK2, which is present in most patients with myeloproliferative neoplasms (MPNs)-a group of bone marrow diseases that are characterized by the over-production of mature blood cells and by an increased risk of developing leukemia. Using a unique mathematical modeling approach, carried out in collaboration with Professor Ben Simons at the Cavendish Laboratory in Cambridge, in combination with experiments on single mouse stem cells, the researchers identified a distinct cellular mechanism that operates in stem cells but not in their daughter cells.  "This study is an excellent example of an inter-disciplinary collaboration pushing the field forward," says lead author Dr David Kent. "Combining mathematical modeling with a large number of single stem cell assays allowed us to predict which cells lose their ability to expand.