ObjectiveTo evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph‐negative MPN patients with atypical variants of JAK2, MPL, or CALR.MethodsWe collected a total of 359 Ph‐negative MPN patients with classical mutations in driver genes JAK2, MPL, or CALR, and divided them into two groups based on whether they had additional atypical variants of driver genes JAK2, MPL, or CALR: 304 patients without atypical variants of driver genes and 55 patients with atypical variants of driver genes. We analyzed the relevant characteristics of these patients.ResultsThis study included 359 patients with Ph‐negative MPNs with JAK2, MPL, or CALR classical mutations and found that 55 (15%) patients had atypical variants of JAK2, MPL, or CALR. Among them, 28 cases (51%) were male, and 27 (49%) were female, with a median age of 64 years (range, 21–83). The age of ET patients with atypical variants was higher than that of ET patients without atypical variants [70 (28–80) vs. 61 (19–82), p = 0.03]. The incidence of classical MPL mutations in ET patients with atypical variants was higher than in ET patients without atypical variants [13.3% (2/15) vs. 0% (0/95), p = 0.02]. The number of gene mutations in patients with atypical variants of driver genes PV, ET, and Overt‐PMF is more than in patients without atypical variants of PV, ET, and Overt‐PMF [PV: 3 (2–6) vs. 2 (1–7), p < 0.001; ET: 4 (2–8) vs. 2 (1–7), p < 0.05; Overt‐PMF: 5 (2–9) vs. 3 (1–8), p < 0.001]. The incidence of SH2B3 and ASXL1 mutations were higher in MPN patients with atypical variants than in those without atypical variants (SH2B3: 16% vs. 6%, p < 0.01; ASXL1: 24% vs. 13%, p < 0.05).ConclusionThese data indicate that classical mutations of JAK2, MPL, and CALR may not be completely mutually exclusive with atypical variants of JAK2, MPL, and CALR. In this study, 30 different atypical variants of JAK2, MPL, and CALR were identified, JAK2 G127D being the most common (42%, 23/55). Interestingly, JAK2 G127D only co‐occurred with JAK2V617F mutation. The incidence of atypical variants of JAK2 in Ph‐negative MPNs was much higher than that of the atypical variants of MPL and CALR. The significance of these atypical variants will be further studied in the future.

中文翻译：

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具有 JAK2、MPL 或 CALR 非典型变异的 Ph 阴性 MPN 患者的临床实验室特征和基因突变谱

目的评估该病的发病率、临床实验室特征和基因突变谱。博士学位‐阴性 MPN 患者，具有非典型变异贾克2,多普勒， 或者卡拉尔.方法我们一共收集了359个博士学位‐具有驱动基因经典突变的阴性 MPN 患者贾克2,多普勒， 或者卡拉尔，并根据它们是否具有额外的非典型驱动基因变异将它们分为两组贾克2,多普勒， 或者卡拉尔：304 名不具有驱动基因非典型变异的患者和 55 名具有非典型驱动基因变异的患者。我们分析了这些患者的相关特征。结果本研究纳入了 359 名患有以下疾病的患者：博士学位‐负 MPN贾克2,多普勒， 或者卡拉尔经典突变，发现 55 名 (15%) 患者具有非典型突变贾克2,多普勒， 或者卡拉尔。其中，男性28例（51%），女性27例（49%），中位年龄64岁（范围21-83岁）。具有非典型变异的 ET 患者的年龄高于无非典型变异的 ET 患者 [70 (28–80) vs. 61 (19–82)，p= 0.03]。古典主义的发生率多普勒具有非典型变异的 ET 患者的突变率高于无非典型变异的 ET 患者 [13.3% (2/15) vs. 0% (0/95)，p= 0.02]。具有驱动基因 PV、ET 和 Overt-PMF 非典型变异的患者的基因突变数量多于不具有 PV、ET 和 Overt-PMF 非典型变异的患者 [PV：3 (2-6) vs. 2 (1–7),p< 0.001；加时赛：4 (2–8) vs. 2 (1–7)，p< 0.05；公开-PMF：5 (2–9) 与 3 (1–8)，p< 0.001]。发病率SH2B3和ASXL1具有非典型变异的 MPN 患者的突变率高于无非典型变异的患者（SH2B3：16% 与 6%，p< 0.01；ASXL1：24% 与 13%，p< 0.05)。结论这些数据表明经典突变贾克2,多普勒， 和卡拉尔与非典型变体可能并不完全相互排斥贾克2,多普勒， 和卡拉尔。在这项研究中，30种不同的非典型变体贾克2,多普勒， 和卡拉尔被确定，JAK2 G127D最常见（42%，23/55）。有趣的是，JAK2 G127D仅同时发生贾克2V617F突变。非典型变异的发生率贾克2在博士学位‐阴性 MPN 远高于非典型变异多普勒和卡拉尔。这些非典型变异的意义将在未来进一步研究。