CALR-mutated myeloproliferative neoplasms.

Calreticulin (CALR) is a chaperone protein that plays a crucial role in protein folding quality control and calcium homeostasis. Mutations in CALR result in a mutated protein lacking key calcium-binding sites and the KDEL sequence, leading to a constitutive activation of the MPL-JAK2-STAT5 pathway, which is involved in the pathogenesis of essential thrombocythemia (ET) and primary myelofibrosis (PMF). Despite advancements in understanding the role of CALR mutations, current therapeutic strategies remain focused on managing symptoms and complications, with allogeneic stem cell transplantation (alloHSCT) as the only curative option. Emerging research is exploring novel immunotherapeutic approaches targeting mutant CALR, including the development of anti-CALR antibodies and T-cell receptor-mediated therapies, offering potential new avenues for treatment in CALR-mutated MPNs. In this review, we will discuss on the role of CALR in MPNs, focusing on its biological structure and its implications on the prognosis and treatment of essential thrombocythemia and primary myelofibrosis.