Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Genes (Basel). 2022 Mar 10;13(3):492. doi: 10.3390/genes13030492.
Introduction: The onset of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is caused by acquired somatic mutations in target myeloid genes “driver mutations”. The CCL2 gene is overexpressed by non-Hodgkin lymphomas and multiple solid tumors. Aim of the study: to evaluate the possible association of CCL2 rs1024611 SNP and its expression level and the risk of developing Philadelphia-negative MPNs. Patients and methods: A total of 128 newly diagnosed Philadelphia-negative MPN patient and 141 healthy subjects were evaluated for the genotype distribution of CCL2 rs1024611 and CCL2 expression levels. Results: The CCL2 rs1024611 G/G genotype was more frequent and significantly frequent among PMF and Post-PV/ET-MF patients and the mean CCL2 expression levels were significantly higher in PMF and Post-PV/ET-MF compared to the healthy subjects. The CCL2 rs1024611 SNP was significantly correlated to the CCL2 gene expression level and fibrosis grade. ROC analysis for the CCL2 gene expression level that discriminates MF patients from PV + ET patients revealed a sensitivity of 80.43% and a specificity of 73.17% with an AUC of 0.919 (p < 0.001). Conclusion: The CCL2 rs1024611 polymorphism could be an independent risk factor for developing MF (PMF and Post-PV/ET-MF). Moreover, CCL2 gene expression could be potential genetic biomarker of fibrotic progression.
费城染色体阴性骨髓增殖性肿瘤（MPN）的发病是由靶向髓系基因的获得性体细胞突变“驱动突变”引起的。CCL2 基因在非霍奇金淋巴瘤和多种实体瘤中过表达。目的：评估 CCL2 rs1024611 SNP 及其表达水平与发生费城阴性 MPN 的风险之间可能存在的关联。患者和方法：共评估了 128 例新诊断的费城阴性 MPN 患者和 141 例健康对照者的 CCL2 rs1024611 基因型分布和 CCL2 表达水平。结果：CCL2 rs1024611 G/G 基因型在 PMF 和 Post-PV/ET-MF 患者中更为常见，且频率显著增高，PMF 和 Post-PV/ET-MF 患者的 CCL2 表达水平明显高于健康对照者。CCL2 rs1024611 SNP 与 CCL2 基因表达水平和纤维化程度显著相关。用于区分 MF 患者和 PV+ET 患者的 CCL2 基因表达水平的 ROC 分析显示，敏感性为 80.43%，特异性为 73.17%，AUC 为 0.919（p<0.001）。结论：CCL2 rs1024611 多态性可能是 MF（PMF 和 Post-PV/ET-MF）发生的独立危险因素。此外，CCL2 基因表达可能是纤维化进展的潜在遗传生物标志物。
