Walter and Eliza Hall Institute scientists have revealed new details about how cell signalling is controlled in the immune system, identifying in the process potential new therapeutic targets for treating severe blood disorders.
Dr Jeff Babon and Professor Nick Nicola, from the institute's Structural Biology and Cancer and Haematology divisions respectively, study interactions between internal cell signalling proteins called JAKs (Janus kinases) and SOCS (Suppressors of Cytokine Signalling).
Dr Babon said the proteins were essential for blood system maintenance and immune responses.
"JAK proteins are activated in response to blood cell hormones called cytokines and instruct immune cells to respond to infection and inflammation," Dr Babon said. "SOCS proteins were discovered at the institute in the early 2000s, and provide a necessary 'negative feedback' response that stops JAKs becoming overactive, which can lead to disease."
Dr Babon said mutations in one particular protein, JAK2, are strongly associated with the development of myeloproliferative diseases.
"When JAK2 is mutated, it tells cells to continually multiply. An excessive amount of blood cells of one type are produced, and the bone marrow is overrun, leading to problems with production of other cell types, and eventually bone marrow failure," Dr Babon said.
Myeloproliferative diseases, such as polycythemia vera and essential thrombocytopenia, are serious blood disorders in which an excessive number of blood cells accumulate in the bone marrow. They can be very severe and sometimes fatal, and may progress to acute leukaemias.