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首页> 美国卫生研究院文献>Stem Cell Investigation >Calreticulin (CALR) mutation in myeloproliferative neoplasms (MPNs)
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Calreticulin (CALR) mutation in myeloproliferative neoplasms (MPNs)

机译：骨髓增生性肿瘤（MPN）中的钙网蛋白（CALR）突变

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As a heterogeneous group of disease, myeloproliferative neoplasms (MPNs) have confused hematologists and hematopathologists with their protean clinical presentations and myriads of morphologies. A thought of classifying MPNs based on molecular alterations has gained popularity because there is increasing evidence that molecular or chromosomal alterations have a better correlation with clinical presentation, response to therapies, and prognosis than conventional morphological classification. This type of efforts has been facilitated by the advancement of molecular technologies. A significant number of gene mutations have been identified in MPNs with JAK2 and MPL being the major ones. However, a significant gap is present in that many cases of MPNs do not harbor any of these mutations. This gap is recently filled by the discovery of Calreticulin (CALR) mutation in MPNs without JAK2 or MPL mutation and since then, the clinical and molecular correlation in MPNs has become a hot research topic. There seems to be a fairly consistent correlation between CALR mutation and certain hematological parameters such as a high platelet count and a better prognosis in MPNs with CALR mutation. However, controversies are present regarding the risks of thrombosis, interactions of CALR with other gene mutation, the role of CALR in the pathogenesis, and the optimal treatment strategies. In addition, there are many questions remain to be answered, which all boiled down to the molecular mechanisms by which CALR causes or contributes to MPNs. Here, we summarized current published literatures on CALR mutations in MPNs with an emphasis on the clinical-molecular correlation. We also discussed the controversies and questions remain to be answered.
机译：作为一种异质性疾病，骨髓增生性肿瘤（MPN）使血液学家和血液病理学家混淆了其纯净的临床表现和无数种形态。基于分子改变对MPN​​s进行分类的想法越来越受欢迎，因为越来越多的证据表明，分子或染色体改变与临床表现，对治疗的反应和预后相比，具有比常规形态学分类更好的关联性。分子技术的发展促进了这种努力。在MPN中已鉴定出大量基因突变，其中JAK2和MPL是主要的。但是，由于许多MPN病例没有任何这些突变，因此存在明显的差距。最近，在没有JAK2或MPL突变的MPN中发现钙网蛋白（CALR）突变，填补了这一空白，从那时起，MPN的临床和分子相关性就成为一个热门研究课题。在具有CALR突变的MPN中，CALR突变与某些血液学参数（例如高血小板计数和更好的预后）之间似乎存在相当一致的相关性。但是，关于血栓形成的风险，CALR与其他基因突变的相互作用，CALR在发病机理中的作用以及最佳治疗策略等方面存在争议。此外，还有许多问题有待解答，这些问题都归结为CALR引起或促成MPN的分子机制。在这里，我们总结了有关MPN中CALR突变的最新出版文献，重点是临床分子相关性。我们还讨论了争议，还有待回答的问题。

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