Araki Marito
Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University.
Rinsho Ketsueki. 2020;61(8):937-944. doi: 10.11406/rinketsu.61.937.
This review aimed to evaluate the molecular mechanism underlying the development of myeloproliferative neoplasms (MPN) caused by mutant calreticulin (CALR). This mutation is found in a subset of patients with Philadelphia chromosome-negative MPNs, and it encodes a molecular chaperone. However, it is essentially impossible to elucidate the oncogenic property of mutant CALR from the wild-type CALR function. Studies have reported that mutant CALR forms a homomultimeric complex via intermolecular interaction between novel domains acquired due to a frameshift mutation, gains a high binding affinity for myeloproliferative leukemia protein (MPL), the thrombopoietin receptor, through a presumptive structural change, and acts as an agonist for MPL. In this review, I would like to describe the course of the discovery of this unique molecular mechanism and discuss future scope of research on mutant CALR.
本综述旨在评估由突变型钙网蛋白（CALR）引起的骨髓增殖性肿瘤（MPN）发生发展的分子机制。这种突变在一部分费城染色体阴性的MPN患者中被发现，它编码一种分子伴侣。然而，从野生型CALR的功能来阐明突变型CALR的致癌特性基本上是不可能的。研究报告称，突变型CALR通过移码突变获得的新结构域之间的分子间相互作用形成同多聚体复合物，通过假定的结构变化获得对血小板生成素受体——骨髓增殖性白血病蛋白（MPL）的高结合亲和力，并作为MPL的激动剂发挥作用。在本综述中，我将描述这一独特分子机制的发现过程，并讨论突变型CALR未来的研究范围。
