CALR mutations and human myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are chronic myeloid malignancies predominantly affecting older individuals and are associated with an increased risk of thrombosis and acute leukaemia. They provide a powerful approach to studying mechanisms whereby stem and progenitor cells, which are inaccessible in other malignancies, are subverted in the earliest stages of tumorigenesis. Professor Green has identified that somatic calreticulin (CALR) mutations reveal a novel biological pathway that modulates haematopoiesis, and that CALR is a target for tumorigenic mutations. During his award Professor Green intends to explore the function of CALR mutations in order to shed new light on normal haematopoiesis (particularly haematopoietic stem cell behaviour and megakaryopoiesis), MPN pathogenesis and calreticulin function.