Calreticulin in Myeloproliferative Neoplasms: The Other Side of the Alice Mirror - European Medical Journal

Calreticulin in Myeloproliferative Neoplasms: The Other Side of the Alice Mirror

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Lilian Varricchio, *Anna Rita Migliaccio

No potential conflict of interest.

EMJ Hema. ;1[1]:114-122. DOI/10.33590/emjhematol/10313345.
Myeloproliferative neoplasms, calreticulin, JAK2, glucocorticoid receptor.

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Calreticulin (CALR), a Ca2+ binding protein mostly localised in the endoplasmic reticulum, regulates Ca2+ homeostasis, chaperones, and other proteins to the nucleus and other cellular compartments. CALR has been implicated in several cellular processes including: signalling, regulation of gene expression, cell adhesion, apoptosis, autoimmunity, and, when expressed on the cell surface, induction of phagocytosis by macrophages. Reports indicating over-expression of CALR in cancer cells suggest that modulation of CALR expression may be exploited to increase their clearance by the immune system. In the hematopoietic system, CALR has been implicated in the activation of the stress pathway as an obligatory partner of the glucocorticoid receptor. More recently, somatic loss-of-function mutations in the CALR gene were discovered in a significant proportion of patients with Philadelphia-negative myeloproliferative neoplasms (MPN) who did not harbour gain-of-function mutations in Janus kinase 2 (JAK2), the first signalling element of cytokine receptors, and myeloproliferative leukaemia virus oncogene (MPL), the thrombopoietin receptor, usually associated with these diseases. This review will summarise current knowledge on the biological activity of CALR and MPL/JAK2 in hematopoiesis, delineate a unifying pathway for the pathogenesis of MPN, and discuss how this pathway may be exploited for therapy.

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