Somatic mutations of calreticulin in myeloproliferative neoplasms

• Published in: International journal of hematology Vol. 105; no. 6; pp. 743 - 747
• Main Authors: Imai, Misa, Araki, Marito, Komatsu, Norio
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.06.2017; Springer Nature B.V
• Subjects: Calreticulin - genetics; Calreticulin - metabolism; Deletion; Endoplasmic reticulum; Exons; Frameshift Mutation; Hematologic Neoplasms - genetics; Hematologic Neoplasms - metabolism; Hematology; Humans; Medicine; Medicine & Public Health; Mutation; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms; Oncology; Pathogenesis; Progress in Hematology; Protein Domains; Tumors; MPL; Calreticulin; Thrombopoietin receptor; Autocrine; Chaperone; Myeloproliferative neoplasms
• DOI: 10.1007/s12185-017-2246-9
• ISSN: 0925-5710

Recurrent somatic mutations in calreticulin ( CALR ) gene that encodes a molecular chaperone residing in the endoplasmic reticulum were identified in 2013 in a subset of patients with myeloproliferative neoplasms (MPNs). All of these mutations found in patients were either small insertion or deletion in a narrow region on exon 9 of CALR gene, and caused +1 frameshift in the reading frame for the translation of the carboxyl-terminus of CALR. Because of this unique feature, the CALR mutation is believed to be a gain-of-function mutation. However, there was essentially no rationale model to implicate the involvement of mutant CALR in the pathogenesis of MPN or other malignancies. Based on the recent findings, this review summarizes a novel molecular mechanism by which this mutant molecular chaperone constitutively activates the cytokine receptor to induce cellular transformation in MPNs.