背景:原发性血小板增多症(ET)涉及巨核细胞和血小板的增殖,并与血栓形成的风险增加有关。我们旨在评估具有表观遗传调节突变的患者的血栓形成风险,并建立模型来预测ET中的血栓形成。
方法:这项队列研究招募了2002年1月至2019年12月在Songklanakarind医院诊断为ET的年龄>15岁的患者。25个靶向基因突变,包括体细胞驱动突变(JAK2,CALR,MPL),表观遗传调节突变(TET2,DNMT3A,IDH1,IDH2,TET2,ASXL1,EZH2,SF3B1,SRSF2)和其他与骨髓肿瘤相关的基因,使用下一代测序进行鉴定。根据临床情况和影像学检查结果确认血栓事件。使用5种生存模型和复发事件方法分析血栓形成风险.
结果:共纳入96例患者,中位随访时间为6.91年。其中,15例患者总共经历了17次动脉血栓事件。具有JAK2突变和IDH1突变的患者具有最高频率的血栓性事件,具有体细胞驱动突变(17.3%)和表观遗传调节突变(100%)。10年无血栓形成生存率为81.3%(95%置信区间:72.0-91.8%)。在所有模型的多变量分析中,IDH1突变是血栓形成风险的重要因素。普伦蒂斯,威廉,Peterson(PWP)间隙-时间模型是最合适的预测模型。
结论:PWP间隔时间模型是ET患者血栓风险的良好预测模型。IDH1突变是血栓形成的重要危险因素;然而,更大样本量的进一步研究应该证实这一点并提供更多见解.
BACKGROUND: Essential thrombocythemia (ET) involves the proliferation of megakaryocytes and platelets and is associated with an increased risk of thrombosis. We aimed to evaluate thrombotic risks in patients with epigenetic regulator mutations and generate a model to predict thrombosis in ET.
METHODS: This cohort study enrolled patients aged > 15 years diagnosed with ET at the Songklanakarind Hospital between January 2002 and December 2019. Twenty-five targeted gene mutations, including somatic driver mutations (JAK2, CALR, MPL), epigenetic regulator mutations (TET2, DNMT3A, IDH1, IDH2, TET2, ASXL1, EZH2, SF3B1, SRSF2) and other genes relevant to myeloid neoplasms, were identified using next-generation sequencing. Thrombotic events were confirmed based on clinical condition and imaging findings, and thrombotic risks were analyzed using five survival models with the recurrent event method.
RESULTS: Ninety-six patients were enrolled with a median follow-up of 6.91 years. Of these, 15 patients experienced 17 arterial thrombotic events in total. Patients with JAK2 mutation and IDH1 mutation had the highest frequency of thrombotic events with somatic driver mutations (17.3%) and epigenetic regulator mutations (100%). The 10-year thrombosis-free survival rate was 81.3% (95% confidence interval: 72.0-91.8%). IDH1 mutation was a significant factor for thrombotic risk in the multivariate analysis for all models. The Prentice, William, and Peterson (PWP) gap-time model was the most appropriate prediction model.
CONCLUSIONS: The PWP gap-time model was a good predictive model for thrombotic risk in patients with ET. IDH1 mutation was significant risk factors for thrombosis; however, further studies with a larger sample size should confirm this and provide more insight.