CCL2 rs1024611Gene Polymorphism in Philadelphia-Negative Myeloproliferative Neoplasms

Abstract

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.

Activated mesenchymal stem/stromal cells promote myeloid cell differentiation via CCL2/CCR2 signaling

“…CCL2 levels are increased in plasma cells from the BM of patients with MPN compared with those in healthy subjects ( Cominal et al., 2021 ). Among patients with MPN, increased CCL2 expression was observed in those with primary myelofibrosis and post-polycythemia vera/essential thrombocythemia myelofibrosis in which the CCL2 rs1024611 G/G genotype is more frequently observed than in healthy subjects ( Hodeib et al., 2022 ). These findings in patients with MPN imply that MSCs mediate responses to stressors such as disease, aging, and infection, and that MSC-secreted factors help determine the fate of hematopoietic cells.…”

Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms

“…In addition to SNPs that confer higher susceptibility to develop BCR::ABL1 -negative MPNs, SNPs that affect the phenotype, prognosis, and response to therapies of BCR::ABL1 -negative MPNs have been reported and summarized [ 75 ]. Although allelic frequencies are not rare (0.114822 for rs6198, 0.279039 for rs1024611, and 0.444187 for rs2431697 by gnomAD, respectively), a poorer prognosis was observed among patients with PMF harboring both JAK2 V617F and homozygous mutations of rs6198 locating at NR3C1 than those bearing wild-type NR3C1 [ 76 ], rs1024611 at CCL2 strongly correlated to the CCL2 expression and the myelofibrosis grade [ 77 ], and homozygous rs2431697 at miR-146a was associated with myelofibrosis progression [ 78 ]. Furthermore, IL28B rs12979860 homozygous phenotype showed hematologic response in patients with PV treated with interferon-α [ 79 ].…”