Department of Haematology, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
Sci Rep. 2019 Dec 27;9(1):19838. doi: 10.1038/s41598-019-56236-x.
Suspicion of myeloproliferative neoplasms (MPNs) and especially essential thrombocythemia (ET) in primary care is often based solely on blood counts, with patients referred to a haematologist without a thorough evaluation. We retrospectively assessed the role of calreticulin gene (CALR) mutations in the diagnosis of MPN in this population. We studied CALR mutations in 524 JAK2 V617F-negative patients with suspected MPN. Uncommon CALR mutations were confirmed by Sanger sequencing and searched for in the COSMIC or HGMD database. Mutations were defined as frameshift or non-frameshift mutations. CALR mutations were detected in 23 patients (23/524 = 4.4%). Four mutations detected in our study were newly identified mutations. Non-frameshift mutations were detected in two patients. Most patients (380/524 = 72.5%) were diagnosed with secondary conditions leading to blood count abnormalities such as iron deficiency, inflammatory and infectious diseases, malignancy and hyposplenism. Nine patients (9/23 = 39%) were retrospectively diagnosed with ET based on CALR mutation confirmation. Two patients with non-frameshift CALR mutations were diagnosed with reactive thrombocytosis and MPN unclassifiable, respectively. Our study showed that CALR mutations are important, non-invasive diagnostic indicators of ET and can aid in its diagnosis. Moreover, the type of CALR mutation must be accurately defined, as non-frameshift mutations may not be associated with ET. Finally, CALR mutation detection should be reserved for patients with high suspicion of clonal haematological disease.
在初级保健中，对骨髓增殖性肿瘤（MPN），尤其是特发性血小板增多症（ET）的怀疑通常仅基于血液计数，患者未经彻底评估就被转介给血液科医生。我们回顾性评估了钙网织蛋白基因（CALR）突变在该人群中诊断 MPN 的作用。我们研究了 524 例 JAK2 V617F 阴性疑似 MPN 患者的 CALR 突变。罕见的 CALR 突变通过 Sanger 测序确认，并在 COSMIC 或 HGMD 数据库中搜索。突变定义为移码或非移码突变。在 23 例患者（23/524=4.4%）中检测到 CALR 突变。我们研究中检测到的 4 种突变是新发现的突变。在 2 例患者中检测到非移码突变。大多数患者（380/524=72.5%）被诊断为导致血液计数异常的继发性疾病，如缺铁、炎症和感染性疾病、恶性肿瘤和脾功能低下。9 例（9/23=39%）患者根据 CALR 突变确认被回顾性诊断为 ET。2 例非移码 CALR 突变患者分别被诊断为反应性血小板增多症和不能分类的 MPN。我们的研究表明，CALR 突变是 ET 的重要、非侵入性诊断指标，可辅助其诊断。此外，CALR 突变的类型必须准确定义，因为非移码突变可能与 ET 无关。最后，CALR 突变检测应保留给高度怀疑克隆性血液病的患者。
