Analysis of clinical characteristics and risk factors for combined thrombosis in patients with classical myeloproliferative neoplasms with JAK2V617F with ASXL1 and/or TET2 mutations
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摘要: 目的 研究JAK2V617F伴ASXL1(或)TET2突变经典骨髓增殖性肿瘤(myeloproliferative neoplasm，MPN)患者的临床特征及分析合并血栓的危险因素。方法 对2017年1月—2021年3月在郑州大学第一附属医院就诊的符合WHO(2016)诊断分型标准且进行基因检测的初诊MPN患者进行回顾性研究，比较分析JAK2V617F伴ASXL1和(或)TET2基因突变患者的临床特征及合并血栓的危险因素。结果 接受基因突变检测且资料完整的经典MPN患者367例，检出JAK2V617F基因单独突变(JAK2ASXL1-/TET2-)患者211例(A组)，JAK2V617F伴ASXL1突变(JAK2ASXL1+/TET2-)患者21例(B组)，JAK2V617F伴TET2突变(JAK2ASXL1-/TET2+)患者22例(C组)，JAK2V617F伴ASXL1、TET2共突变(JAK2ASXL1+/TET2+)17例(D组)，共计271例。A、B、C、D 4组患者性别、初诊时WBC、HGB、中性粒细胞、PLT、LDH、脾大，差异均无统计学意义(P>0.05)，而发病年龄、中性粒细胞计数与淋巴细胞计数比值(NLR)、初诊时血栓史差异有统计学意义(P＜0.05)。高龄(≥60岁)、高WBC值(WBC≥10×109/L)、高HGB水平(男HGB≥160 g/L，女HGB≥150 g/L)、高LDH水平(LDH≥300 U/L)、NLR≥3、高血压及JAK2V617F伴TET2突变的患者均更易发生血栓事件(P＜0.05)。结论 高龄、高WBC值、高HGB水平、高LDH水平、NLR≥3、高血压、PV及伴有ASXL1、TET2突变是经典MPN患者发生血栓事件的危险因素。
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关键词:
- JAK2V617F基因 /
- ASXL1基因 /
- TET2基因 /
- 骨髓增殖性肿瘤 /
- 血栓
Abstract: Objective To study the clinical characteristics and analyze the risk factors for combined thrombosis in patients with classical myeloproliferative neoplasm(MPN) with JAK2V617F with ASXL1 and/or TET2 mutations.Methods A retrospective study was conducted to compare and analyze the clinical characteristics of patients with JAK2V617F with ASXL1 and/or TET2 mutations and the risk factors for combined thrombosis in patients with primary MPN who met the diagnostic typing criteria of WHO(2016) and underwent genetic testing from January 2017 to March 2021 at the First Affiliated Hospital of Zhengzhou University.Results Among 367 patients with classical MPN who underwent mutation testing and had complete data, 211 patients with JAK2V617F gene alone mutation(JAK2ASXL1-/TET2-) were detected(group A), 21 patients with JAK2V617F with ASXL1 mutation(JAK2ASXL1+/TET2-)(group B), 22 patients with JAK2V617F with TET2 mutation(JAK2ASXL1-/TET2+) in 22 patients(group C), and JAK2V617F with ASXL1 and TET2 co-mutation (JAK2ASXL1+/TET2+) in 17 patients(group D), for a total of 271 patients. Sex, WBC at the initial diagnosis, HGB, neutrophils, PLT, and LDH in patients in groups A, B, C, and D were not statistically different, splenomegaly were not statistically different(P>0.05), while the differences in age of onset, neutrophil count-to-lymphocyte count ratio(NLR) and history of thrombosis at initial diagnosis were statistically significant(P < 0.05). Patients with advanced age(≥60 years), high WBC values(WBC≥10×109/L), high HGB levels(male HGB ≥160 g/L, female HGB ≥150 g/L), high LDH levels(LDH ≥300 U/L), NLR ≥3, hypertension, PV and JAK2V617F with ASXL1, TET2 mutation were more likely to have thrombotic events(P < 0.05).Conclusion Advanced age, high WBC value, high HGB level, high LDH level, NLR ≥3, hypertension, PV and with ASXL1 mutation were risk factors for thrombotic events in patients with classical MPN.-
Key words:
- JAK2V617F gene /
- ASXL1 gene /
- TET2 gene /
- myeloproliferative neoplasm /
- thrombosis
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表 1 JAK2V617F伴ASXL1和(或) TET2突变经典MPN患者临床和实验室特征的比较
特征 A组(n=211) B组(n=21) C组(n=22) D组(n=17) P 性别(男/女)/例 95/116 10/11 8/14 9/8 0.76 年龄/岁 62(60~64) 58(49~66) 55(50~60)1) 55(50~61)1) 0.01 WBC/(×109/L) 14.52 (13.00~16.04) 12.51 (7.12~17.89) 12.70 (9.30~16.10) 12.71 (8.54~16.89) 0.43 HGB/(g/L) 146(140~152) 130(106~154)2) 158(137~178) 134(107~161) 0.22 PLT/(×109/L) 740(661~819) 761(477~1 044) 655(442~889) 846(379~1 313) 0.83 LDH/(U/L) 344(320~367) 327(247~407) 296(227~365) 338(229~447) 0.55 NLR 7(6~8) 4(3~5)1) 7(5~8) 6(3~8) 0.01 PLR 429(385~473) 419(257~581) 505(275~734) 516(206~826) 0.80 脾大/例 75 5 11 8 0.25 血栓事件/例(%) 102(48.3) 5(23.8)1) 13(59.1) 12(70.6)2) 0.02 动脉血栓/例 脑血管事件 69 2 8 4 0.13 心血管事件 25 1 2 4 0.33 其他 7 2 3 3 0.02 静脉血栓/例 1 0 0 1 0.08 MPN亚型(PV/ET/MF)/例 65/117/29 6/10/5 10/8/4 4/8/5 0.33 中位随访时间/月 67(66~69) 54(44~63) 50(48~53) 35(29~41) ＜0.01 与A组比较，1)P＜0.05；与B组比较，2)P＜0.05。 
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表 2 BCR-ABL阴性经典MPN患者有无血栓事件的临床比较
例(%) 特征 观察组(n=132) 对照组(n=139) χ2 P 性别 59(44.7) 63(45.3) 0.971 >0.99 年龄≥60岁 89(67.4) 64(46.0) 12.591 ＜0.01 WBC≥10×109/L 88(66.7) 73(52.5) 5.602 0.02 高HGB水平 68(51.5) 39(28.1) 15.592 ＜0.01 PLT≥450×109/L 93(70.5) 89(64.0) 1.267 0.30 LDH≥300 U/L 81(61.4) 67(48.2) 4.732 0.04 NLR≥3 110(83.3) 98(70.5) 6.246 0.01 高血压 70(53.0) 40(28.8) 16.515 ＜0.01 糖尿病 11(8.3) 11(7.9) 0.016 >0.99 肝大 2(1.5) 1(0.7) 0.392 0.61 脾大 45(34.1) 54(38.9) 0.661 0.42 MPN亚型 12.591 ＜0.01 PV 53(40.2)1) 32(23.0)1) ET 68(51.5) 75(54.0) PMF 11(8.3)1) 32(23.0)1) 基因型 9.371 0.02 JAK2ASXL1-/TET2- 102(77.3)2) 109(78.4)2) JAK2ASXL1+/TET2- 5(3.8) 16(11.5) JAK2ASXL1-/TET2+ 13(9.8) 9(6.5) JAK2ASXL1+/TET2+ 12(9.1)2) 5(3.6) 与ET比较，1)P＜0.05；与JAK2ASXL1+/TET2-组比较，2)P＜0.05。
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