ASXL1 mutations in Chinese patients with essential thrombocythemia.
ASXL1 mutations in Chinese patients with essential thrombocythemia.
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中国原发性血小板增多症患者ASXL1突变
DOI：
10.3892/etm.2018.5939
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发表时间：
2018-05
影响因子：
2.7
通讯作者：
Zuo XL
中科院分区：
文献类型：
--
作者：
Nie YB;Sun M;He CK;Ju MK;Zhou FL;Wu SY;Zhou Y;Liu L;Shen H;Huang TT;Liu P;Xu Y;Shao L;Zuo XL
原发性血小板增多症（ET）以血栓和出血事件为特征。中国ET患者的临床特征与这些患者中额外性梳样1（ASXL1）突变的关联仍有待阐明。在本研究中，纳入了72例新诊断的中国ET患者以确定ASXL1突变。使用桑格测序法检测ASXL1、Janus激酶（JAK）2、钙网蛋白（CALR）和骨髓增殖性白血病（MPL）基因的突变，并对数据进行统计学分析。ET患者中ASXL1、JAK2 V617F、CALR和MPL W515突变的频率分别为19.4%（14/72）、29.2%（21/72）、31.9%（23/72）和0%（0/72）。值得注意的是，28例ET患者（38.9%）JAK2、CALR和MPL突变均为阴性；这些患者被归类为三阴性（TN）。JAK2 V617F、CALR和TN突变患者中ASXL1突变的频率分别为23.8%（5/21）、21.7%（5/23）和14.3%（4/28）。与ASXL1野生型（wt）队列相比，ASXL1突变患者表现出明显的血栓事件倾向（42.9%对12.1%；P = 0.021）。此外，JAK2 V617F突变患者的平均年龄高于CALR突变患者（64.76岁对52.96岁；P = 0.008）或TN患者（64.76岁对51.14岁；P = 0.002）。再者，与TN患者相比，JAK2 V617F突变患者外周血（PB）中白细胞更多（12.40×10⁹/L对8.20×10⁹/L；P = 0.02）。此外，CALR突变患者外周血中的血小板（PLT）比JAK2 V617F突变患者更多（787.91×10⁹/L对562.17×10⁹/L；P = 0.047）。与CALR或JAK2 V617F突变患者相比，TN患者临床症状（包括头晕、心悸和胸闷）的发生率显著较低（14.1%对39.1%；P = 0.043以及14.1%对38.1%；P = 0.050）。ASXL1突变患者和ASXL1野生型患者之间无进展生存期无显著差异（P = 0.590）。总之，ASXL1突变的ET患者容易发生血栓事件。CALR突变、JAK2 V617F突变和TN患者之间血栓事件的发生无显著差异。此外，ASXL1突变/TN患者的血小板数量比ASXL1/JAK2 V617F双突变患者更多。因此，ASXL1突变可能是ET患者发生血栓事件的一个危险因素。
Essential thrombocythemia (ET) is characterized by thrombotic and hemorrhagic events. The association of clinical characteristics of Chinese ET patients and additional sex combs like 1 (ASXL1) mutations in these patients has remained to be elucidated. In the present study, 72 newly diagnosed Chinese ET patients were enrolled to determine ASXL1 mutations. Mutations in ASXL1, Janus kinase (JAK)2, calreticulin (CALR) and myeloproliferative leukemia (MPL) genes were detected using Sanger sequencing, and data were statistically analyzed. The frequencies of ASXL1, JAK2 V617F, CALR and MPL W515 mutations in ET patients were 19.4% (14/72), 29.2% (21/72), 31.9% (23/72) and 0% (0/72), respectively. Of note, 28 ET patients (38.9%) were negative for JAK2, CALR and MPL mutations; these patients were classified as triple-negative (TN). The frequency of ASXL1 mutations in patients with JAK2 V617F, CALR and TN mutations was 23.8% (5/21), 21.7% (5/23) and 14.3% (4/28), respectively. ASXL1-mutant patients exhibited significant propensities for thrombotic events compared with the ASXL1 wild-type (wt) cohort (42.9 vs. 12.1%; P=0.021). In addition, JAK2 V617F-mutant patients had a higher mean age compared with CALR-mutant (64.76 vs. 52.96 years; P=0.008) or TN patients (64.76 vs. 51.14 years; P=0.002). Furthermore, more white blood cells in the peripheral blood (PB) were observed in JAK2 V617F-mutant patients compared with those in TN patients (12.40 vs. 8.20×109/l; P=0.02). In addition, CALR-mutant patients exhibited more platelets (PLT) in PB than JAK2 V617F-mutant patients (787.91 vs. 562.17×109/l; P=0.047). TN patients had a significantly lower incidence of clinical symptoms, including dizziness, palpitation and chest congestion compared with CALR- or JAK2 V617F-mutant patients (14.1 vs. 39.1%; P=0.043 and 14.1 vs. 38.1%; P=0.050). No significant difference in progression-free survival was observed between ASXL1-mutant and ASXL1-wt patients (P=0.590). In conclusion, ASXL1-mutant ET patients are prone to experiencing thrombotic events. There was no significant difference in the occurrence of thrombotic events among CARL-mutant, JAK2 V617F-mutant and TN patients. Furthermore, ASXL1-mutant/TN patients exhibited a higher number of PLT than ASXL1/JAK2 V617F-double mutant patients. Therefore, ASXL1 mutations may be a risk factor for the occurrence of thrombotic events in ET patients.