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Abstract：
OBJECTIVE: To evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR.
METHODS: We 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.
RESULTS: This 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).
CONCLUSIONS: These 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.
METHODS: We 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.
RESULTS: This 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).
CONCLUSIONS: These 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.
摘要：
目的：为了评估发病率，临床实验室特征，以及具有JAK2、MPL非典型变异的Ph阴性MPN患者的基因突变谱,或CALR。
方法：我们共收集了359例Ph阴性MPN患者，这些患者的驱动基因JAK2，MPL，或CALR，并根据他们是否有驱动基因JAK2，MPL的其他非典型变异将他们分为两组，或CALR：304例无驱动基因非典型变异的患者和55例有驱动基因非典型变异的患者。我们分析了这些患者的相关特征。
结果：本研究包括359例Ph阴性MPNs伴JAK2、MPL、或CALR经典突变，发现55（15％）患者有JAK2，MPL，或CALR。其中,28例（51％）为男性，和27（49％）是女性，年龄中位数为64岁(范围，21-83).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]。具有非典型变异的ET患者中经典MPL突变的发生率高于无非典型变异的ET患者[13.3%(2/15)vs.0%（0/95），p=0.02]。驱动基因PV的非典型变异患者的基因突变数量，ET,Overt-PMF比没有非典型PV变异的患者更多，ET,和Overt-PMF[PV：3（2-6）与2（1-7）p<0.001；ET：4（2-8）与2（1-7）p<0.05；Overt-PMF：5（2-9）vs.3（1-8）p<0.001]。具有非典型变异的MPN患者中SH2B3和ASXL1突变的发生率高于没有非典型变异的患者（SH2B3：16％vs.6%,p<0.01；ASXL1：24%vs.13%,p<0.05)。
结论：这些数据表明JAK2，MPL，和CALR可能与JAK2、MPL、和CARR。在这项研究中,JAK2，MPL的30种不同的非典型变体，和CARR被确认,JAK2G127D是最常见的(42%，23/55)。有趣的是,JAK2G127D仅与JAK2V617F突变共同发生。Ph阴性MPN中JAK2非典型变异的发生率远高于MPL和CALR的非典型变异。这些非典型变异的意义将在未来进一步研究。
方法：我们共收集了359例Ph阴性MPN患者，这些患者的驱动基因JAK2，MPL，或CALR，并根据他们是否有驱动基因JAK2，MPL的其他非典型变异将他们分为两组，或CALR：304例无驱动基因非典型变异的患者和55例有驱动基因非典型变异的患者。我们分析了这些患者的相关特征。
结果：本研究包括359例Ph阴性MPNs伴JAK2、MPL、或CALR经典突变，发现55（15％）患者有JAK2，MPL，或CALR。其中,28例（51％）为男性，和27（49％）是女性，年龄中位数为64岁(范围，21-83).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]。具有非典型变异的ET患者中经典MPL突变的发生率高于无非典型变异的ET患者[13.3%(2/15)vs.0%（0/95），p=0.02]。驱动基因PV的非典型变异患者的基因突变数量，ET,Overt-PMF比没有非典型PV变异的患者更多，ET,和Overt-PMF[PV：3（2-6）与2（1-7）p<0.001；ET：4（2-8）与2（1-7）p<0.05；Overt-PMF：5（2-9）vs.3（1-8）p<0.001]。具有非典型变异的MPN患者中SH2B3和ASXL1突变的发生率高于没有非典型变异的患者（SH2B3：16％vs.6%,p<0.01；ASXL1：24%vs.13%,p<0.05)。
结论：这些数据表明JAK2，MPL，和CALR可能与JAK2、MPL、和CARR。在这项研究中,JAK2，MPL的30种不同的非典型变体，和CARR被确认,JAK2G127D是最常见的(42%，23/55)。有趣的是,JAK2G127D仅与JAK2V617F突变共同发生。Ph阴性MPN中JAK2非典型变异的发生率远高于MPL和CALR的非典型变异。这些非典型变异的意义将在未来进一步研究。
