Inserm, U970, Paris Cardiovascular Research Center - PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France.
J Hepatol. 2017 Sep;67(3):501-507. doi: 10.1016/j.jhep.2017.04.021. Epub 2017 May 5.
Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). Janus kinase 2 gene (JAK2) mutations are found in 80 to 90% of patients with SVT and MPN. Mutations of the calreticulin (CALR) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing is questionable. This study aimed to identify a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing.
CALR, JAK2 and thrombopoietin receptor gene (MPL) mutations were analysed in a test cohort that included 312 patients with SVT. Criteria to identify patients at high risk of CALR mutations in this test cohort was used and evaluated in a validation cohort that included 209 patients with SVT.
In the test cohort, 59 patients had JAK2, five had CALR and none had MPL mutations. Patients with CALR mutations had higher spleen height and platelet count than patients without these mutations. All patients with CALR mutations had a spleen height ⩾16cm and platelet count >200×10/L. These criteria had a positive predictive value of 56% (5/9) and a negative predictive value of 100% (0/233) for the identification of CALR mutations. In the validation cohort, these criteria had a positive predictive value of 33% (2/6) and a negative predictive value of 99% (1/96).
CALR mutations should be tested in patients with SVT, a spleen height ⩾16cm, platelet count >200×10/L, and no JAK2. This strategy avoids 96% of unnecessary CALR mutations testing. Lay summary: Mutations of the CALR gene are detected in 0 to 2% of patients with SVT, thus the utility of systematic CALR mutation testing to diagnose MPN is questionable. This study demonstrates that CALR mutations testing can be restricted to patients with SVT, a spleen height ⩾16cm, a platelet count >200×10/L, and no JAK2. This strategy avoids 96% of unnecessary CALR mutations testing.
骨髓增殖性肿瘤（MPN）是导致脾静脉血栓形成（SVT）的主要原因。80%至 90%的 SVT 和 MPN 患者存在 Janus 激酶 2 基因（JAK2）突变。钙网蛋白（CALR）基因突变也有报道。然而，由于其患病率为 0 至 2%，因此常规检测的实用性值得怀疑。本研究旨在确定一组 SVT 患者，这些患者存在 CALR 突变的风险较高，因此需要进行这种基因检测。
在包括 312 例 SVT 患者的测试队列中分析了 CALR、JAK2 和血小板生成素受体基因（MPL）突变。在包括 209 例 SVT 患者的验证队列中使用了确定该测试队列中 CALR 突变高危患者的标准，并对其进行了评估。
在测试队列中，59 例患者存在 JAK2 突变，5 例患者存在 CALR 突变，无一例患者存在 MPL 突变。CALR 突变患者的脾脏高度和血小板计数高于未发生这些突变的患者。所有 CALR 突变患者的脾脏高度均≥16cm，血小板计数>200×10/L。这些标准对 CALR 突变的阳性预测值为 56%（9/16），阴性预测值为 100%（233/233）。在验证队列中，这些标准的阳性预测值为 33%（6/18），阴性预测值为 99%（96/97）。
应在 SVT、脾脏高度≥16cm、血小板计数>200×10/L、无 JAK2 的患者中检测 CALR 突变。该策略可避免 96%的不必要的 CALR 突变检测。
CALR 基因突变在 0 至 2%的 SVT 患者中被检测到，因此系统地进行 CALR 基因突变检测以诊断 MPN 的实用性值得怀疑。本研究表明，CALR 基因突变检测可仅限于 SVT、脾脏高度≥16cm、血小板计数>200×10/L、无 JAK2 的患者。该策略可避免 96%的不必要的 CALR 突变检测。
