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.

Background: Netrin-1 is a laminin like protein highly induced after acute and chronic kidney injury, represent tubular damage and excreted in urine of both animals and humans. Netrin-1 is a potential biomarker predicting the development of diabetic kidney disease. Interleukin-6 (IL-6) is an inflammatory cytokine that has a role in the transformation from acute to chronic inflammation. The aim of this work was to evaluate the role of Netrin-1 and IL-6 in the development of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods: Our study included 75 patients with T2DM and 25 healthy control group. The study duration started from October 2019 to January 2021. Participants were subdivided into four equal groups: group I: 25 healthy subjects as control group, group II: 25 diabetic patients with albumin/creatinine ratio < 30 mg/g, group III: 25 diabetic patients with albumin/creatinine ratio 30-300 mg/g, group IV: 25 diabetic patients with albumin/creatinine ratio > 300 mg/g. All subjects underwent complete clinical examination, laboratory investigations and measurement of serum Netrin-1 and IL-6 by ELISA. Results: Nertin-1 was significantly higher in group III and group IV than group II and control group (P<0.001*). Netrin-1 was positively correlated with IL-6, fasting BG, 2HPP, HbA1C, B. urea, S. creatinine and urinary ACR, but it was negatively correlated with eGFR, Hb and S. albumin. IL-6 was significantly higher in group IV than group III, group II and control group (p<0.001*). There was a positive correlation between IL-6 and 2HPP, HbA1C, B. urea, S. creatinine and urinary ACR, but there was a negative correlation between IL-6 and eGFR, Hb and S. albumin. Netrin-1 was more sensitive 96.5% and more specific 99.8% than IL-6 sensitivity 83.3% and specificity 85.0%. Conclusions: Netrin-1 and IL-6 were significantly higher in diabetic nephropathy patients with macroalbuminuria than other groups. Netrin-1 was more sensitive and specific than IL-6 in predicting DN and its progression.

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 (SKP2) gene may play an essential role in the genesis and progression of CML. Aim of the study: We try to explore the diagnostic/prognostic impact of SKP2 gene expression to predict treatment response in first-line IM-treated CML patients at an early response stage. Patients and methods: The gene expression and protein levels of SKP2 were determined using quantitative RT-PCR and ELISA in 100 newly diagnosed CML patients and 100 healthy subjects. Results: SKP2 gene expression and SKP2 protein levels were significantly upregulated in CML patients compared to the control group. The receiver operating characteristic (ROC) analysis for the SKP2 gene expression level, which that differentiated the CML patients from the healthy subjects, yielded a sensitivity of 86.0% and a specificity of 82.0%, with an area under the curve (AUC) of 0.958 (p < 0.001). The ROC analysis for the SKP2 gene expression level, which differentiated optimally from the warning/failure responses, yielded a sensitivity of 70.59% and a specificity of 71.21%, with an AUC of 0.815 (p < 0.001). Conclusion: The SKP2 gene could be an additional diagnostic and an independent prognostic marker for predicting treatment responses in first-line IM-treated CML patients at an early time point (3 months).