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Mutations in calreticulin are one of the key disease-initiating mutations in myeloproliferative neoplasms (MPN). In MPN, mutant calreticulin translates with a novel C-terminus that leads to aberrant binding to the extracellular domain of the thrombopoietin receptor, MPL. This cell surface neoantigen has become an attractive target for immunological intervention. Here, we summarize recent advances in the development of mutant calreticulin targeting antibodies as a novel therapeutic approach in MPN.