Objective: 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. Methods: 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［M（Q1，Q3）］62 (53, 69) years. The WT1-positive group (n=93) and the WT1-negative group (n=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 [M (Q1, Q3)] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis. Results: 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 P<0.05). Positive correlations were found between WT1 gene expression levels and JAK2V617F gene mutation load, RDW, MPV (r=0.478, 0.346, 0.236, all P<0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (r=-0.339, -0.170, -0.206, -0.388, all P<0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2V617F 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 JAK2V617F, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all P<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 (P=0.883). Logistic regression analysis showed that male (OR=2.41,95%CI:1.02-5.71,P=0.046) and positive JAK2V617F gene mutation (OR=3.96,95%CI:1.50-10.42,P=0.005) were risk factors for thrombotic events in ET patients. Conclusions: 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 JAK2V617F gene mutation are risk factors for thrombotic events in ET patients.
目的： 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。 方法： 回顾性纳入2015年1月至2023年3月武汉大学中南医院252例初诊 MPN患者，其中男128例，女124例，年龄［M（Q1，Q3）］为62（53，69）岁。根据WT1基因表达水平分为WT1阳性组（n=93）和WT1阴性组（n=159），比较两组患者各项临床指标的差异，分析WT1基因在各亚型患者中的表达水平以及与临床特征和血栓事件的相关性。截至2023年3月31日，随访时间［M（Q1，Q3）］为12.0（6.5，21.0）个月。采用logistic 回归分析 MPN患者血栓事件发生的危险因素。 结果： 252例初诊MPN患者总体骨髓样本的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P<0.05）。WT1基因表达水平与JAK2V617F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（r=0.478、0.346、0.236，均P<0.01），与血小板计数（PLT）、淋巴细胞绝对值（LYM）、凝血酶原活动度（PTTA）、乳酸脱氢酶（LDH）呈负相关（r=-0.339、-0.170、-0.206、-0.388，均P<0.01）。与WT1阴性组比较，WT1阳性组患者体质性症状、脾脏肿大、JAK2V617F基因突变阳性比例较高，RDW、LDH、中性粒细胞绝对值（NEUT）和 MPV水平较高，而三阴性（JAK2V617F、CALR及MPL基因突变均阴性）比例较低，PLT、LYM和PTTA水平较低（均P<0.05）。WT1阳性组与WT1阴性组血栓事件发生率分别为32.3%（30/93）、32.1%（51/159），差异无统计学意义（P=0.883）。logistic回归分析显示，男性（OR=2.41，95%CI：1.02~5.71，P=0.046）及JAK2V617F基因突变阳性（OR=3.96，95%CI：1.50~10.42，P=0.005）是ET患者发生血栓事件的危险因素。 结论： WT1基因表达水平增高与MPN患者的疾病进展和转化指标相关。PMF患者WT1基因表达水平增高可作为MPN分型辅助诊断指标，但与血栓事件发生无相关性。男性及JAK2V617F基因突变阳性是ET患者发生血栓事件的危险因素。.