Calreticulin (CALR) is a chaperone present in the endoplasmic reticulum, which is involved in the quality control of N-glycosylated proteins and storage of calcium ions. In 2013, the C-terminal mutation in CALR was identified in half of the patients with essential thrombocythemia and primary myelofibrosis who did not have a JAK2 or MPL mutation. The results of 8 years of intensive research are changing the clinical practice associated with treating myeloproliferative neoplasms (MPNs). The presence or absence of CALR mutations and their mutation types already provide important information for diagnosis and treatment decision making. In addition, the interaction with the thrombopoietin receptor MPL, which is the main mechanism of transformation by CALR mutation, and the expression of the mutant protein on the cell surface have a great potential as targets for molecular-targeted drugs and immunotherapy. This chapter presents recent findings on the clinical significance of the CALR mutation and the molecular basis by which this mutation drives MPNs.

钙网蛋白 (CALR) 是一种存在于内质网中的分子伴侣，参与 N-糖基化蛋白质的质量控制和钙离子的储存。2013 年，在没有JAK2或MPL突变的原发性血小板增多症和原发性骨髓纤维化患者中发现了 CALR 的 C 末端突变。8 年深入研究的结果正在改变与治疗骨髓增生性肿瘤 (MPN) 相关的临床实践。CALR突变的存在与否及其突变类型已经为诊断和治疗决策提供了重要信息。此外，与血小板生成素受体 MPL 的相互作用，这是通过CALR突变以及突变蛋白在细胞表面的表达具有作为分子靶向药物和免疫治疗靶点的巨大潜力。本章介绍了有关CALR突变的临床意义的最新发现以及该突变驱动 MPN 的分子基础。