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[肾母细胞瘤1基因在骨髓增殖性肿瘤患者中的表达水平及其与临床特征的相关性]

[Expression level of Wilms' tumor 1 gene and its correlation with clinical features in patients with myeloproliferative neoplasms].

作者信息

Liu C, Wu S Y, Zhang A B, Luo P, Zhou Y, Liu Y, Zuo X L

机构信息

Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2023 Dec 5;103(45):3658-3664. doi: 10.3760/cma.j.cn112137-20231007-00663.

Abstract

To investigate the expression level of WT1 gene in patients with classical Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) and its correlation with clinical features. A retrospective study included 252 patients with newly diagnosed MPN in Zhongnan Hospital of Wuhan University from January 2015 to March 2023, including 128 males and 124 females, aged[(,)]62 (53, 69) years. The WT1-positive group (=93) and the WT1-negative group (=159) were split based on the level of WT1 gene expression, and the variations in clinical indicators between the two groups were compared. Its levels of expression in each subtype and its relationships to thrombotic events and clinically significant variables were analyzed. As of March 31, 2023, the follow-up period [ (, )] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis. The WT1 gene expression level in the overall bone marrow samples of 252 patients with newly diagnosed MPN was 0.30% (0.10%, 1.10%). The expression level in primary myelofibrosis (PMF) patients was 1.45% (0.41%, 3.24%), which was higher than 0.15% (0.02%, 0.32%), 0.37% (0.16%, 1.09%) in essential thrombocythemia (ET) and polycythemia vera (PV) patients (both <0.05). Positive correlations were found between WT1 gene expression levels and JAK2 gene mutation load, RDW, MPV (=0.478, 0.346, 0.236, all <0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (=-0.339, -0.170, -0.206, -0.388, all <0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2 gene mutation, and higher levels of RDW, LDH, NEUT, and MPV compared to the WT1-negative group. In contrast, the proportion of triple-negative (negative for all three hot mutations of JAK2, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all <0.05). The thrombotic event rates of WT1-positive group and WT1-negative group were 32.3% (30/93) and 32.1% (51/159), respectively, and the difference was not statistically significant (=0.883). Logistic regression analysis showed that male (=2.41,95%:1.02-5.71,=0.046) and positive JAK2 gene mutation (=3.96,95%:1.50-10.42,=0.005) were risk factors for thrombotic events in ET patients. WT1 gene expression is elevated in PMF patients and correlated with indicators of disease progression and transformation in MPN patients. It can be utilized as an auxiliary diagnostic indicator for classical MPN staging but is not correlated with the incidence of thrombotic events. Male and positive JAK2 gene mutation are risk factors for thrombotic events in ET patients.

摘要

探讨WT1基因在经典费城染色体(Ph)阴性骨髓增殖性肿瘤(MPN)患者中的表达水平及其与临床特征的相关性。一项回顾性研究纳入了2015年1月至2023年3月在武汉大学中南医院新诊断的252例MPN患者,其中男性128例,女性124例,年龄[(,)]62(53,69)岁。根据WT1基因表达水平将患者分为WT1阳性组(=93)和WT1阴性组(=159),比较两组临床指标的差异。分析其在各亚型中的表达水平及其与血栓形成事件和临床显著变量的关系。截至2023年3月31日,随访时间[(,)]为12.0(6.5,21.0)个月。采用逻辑回归分析MPN患者血栓形成的危险因素。252例新诊断MPN患者骨髓样本中WT1基因表达水平为0.30%(0.10%,1.10%)。原发性骨髓纤维化(PMF)患者的表达水平为1.45%(0.41%,3.24%),高于原发性血小板增多症(ET)和真性红细胞增多症(PV)患者的0.15%(0.02%,0.32%)、0.37%(0.16%,1.09%)(均<0.05)。WT1基因表达水平与JAK2基因突变负荷、红细胞分布宽度(RDW)、平均血小板体积(MPV)呈正相关(=0.478,0.346,0.236,均<0.01)。而WT1基因表达水平与血小板计数(PLT)、淋巴细胞计数(LYM)、血小板平均寿命(PTTA)、乳酸脱氢酶(LDH)呈负相关(=-0.339,-0.170,-0.206,-0.388,均<0.01)。与WT1阴性组相比,WT1阳性组患者出现躯体症状、脾肿大、JAK2基因突变阳性的比例更高,RDW、LDH、中性粒细胞计数(NEUT)和MPV水平更高。相反,三阴性(JAK2、钙网蛋白(CALR)和髓系血小板生成素受体(MPL)三种热点突变均为阴性)的比例更低,PLT、LYM和PTTA水平更低(均<0.05)。WT1阳性组和WT1阴性组的血栓形成事件发生率分别为32.3%(30/93)和32.1%(51/159),差异无统计学意义(=0.883)。逻辑回归分析显示,男性(=2.41,95%可信区间:1.02 - 5.71,=0.046)和JAK2基因突变阳性(=3.96,95%可信区间:1.50 - 10.42,=0.005)是ET患者血栓形成事件的危险因素。WT1基因在PMF患者中表达升高,与MPN患者疾病进展和转化指标相关。它可作为经典MPN分期的辅助诊断指标,但与血栓形成事件的发生率无关。男性和JAK2基因突变阳性是ET患者血栓形成事件的危险因素。

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