CALR and CD47: An Insight into Their Roles in the Disease Progression of MDS and MPN

Abstract

Myelodysplastic syndrome and myeloproliferative neoplasms are clonal myeloid disorders arising from haematopoietic stem cells that have the tendency to progress into acute myeloid leukaemia. Multiple prognostic scoring systems have been proposed and utilised in clinical practice to predict disease evolution, however none of them can predict treatment response. In solid tumours, the relationship between the pro-phagocytic calreticulin and the anti-phagocytic CD47 is repeatedly investigated. Overexpression of calreticulin has been documented to produce a pro-phagocytic signal in solid tumour and it is often counteracted by a concomitant expression of the anti-phagocytic CD47 as they act in response to one another, reflecting an apoptosis vs survival mechanism in response to chemotherapy. The role of both calreticulin and CD47 are currently poorly understood in myeloid malignancies including myelodysplastic syndrome and myeloproliferative neoplasms. The aim of this review is to elaborate on the current understanding round the roles and implications of calreticulin and CD47 signalling with in solid and haematological cancers, discuss potential roles for calreticulin and CD47 expression in transformation of myeloid cells in patients with MDS or MPN into AML and how these advances are starting to be used to design new therapeutic strategies to determine disease progression and treatment response in both solid cancer and myeloid malignancies.