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Predictive Value of miR-146a rs2431697 Polymorphism to Myelofibrosis Progression in Patients with Myeloproliferative
Salah Aref1, Doaa Atia1, Ahmed Al Tantawy2
1Hematology Unit, Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt.
Background:
Bone marrow myelofibrosis (BMF) that develop on top of Polycythaemia vera (PV) and essential thrombocythemia leads to shortening of the patient's overall survival. This study aimed to address the impact of miR-146a rs2431697 polymorphism on inflammatory biomarkers and genes expression and the hazards of myelofibrosis progression.
Patients And Methods:
The study included 88 myeloproliferative neoplasm (40 PV; 27 ET; 21 MF) and 90 healthy controls. For all investigated subjects miR-146a rs2431697 genotypes were identified by sequencing and the expression of miR-146a; IL-1β; NF-κB; a NOD-like receptor family, pyrin domain containing 3 (NLRP3) (NLRP3) genes were estimated by real time PCR.
Results:
miR146a genotypes revealed that there was significant association between TT and TC genotypes with MF. The degree of miR146a expression was significantly reduced in MF as compared to both PV and ET. In contrast; the levels of IL-1β; NF-κB; NLRP3 genes expression were significantly elevated in MF patients group as compared to PV and ET patients' group. Multivariate analysis identified TT genotype as poor predictor of MF progression.
Conclusion:
miR-146a rs2431697 TT genotype is associated with high risk of MF progression in MPN patients. Targeting of IL-1β; NF-κB; NLRP3 genes might help in hindering of MF progression in MPN patients,
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Insights
The miR-146a rs2431697 TT genotype is linked to a higher risk of myelofibrosis progression in myeloproliferative neoplasm patients. Targeting inflammatory genes like IL-1β, NF-κB, and NLRP3 may help slow this progression.
Area of Science:
- Genetics and Molecular Biology
- Hematology
- Oncology
Background:
- Myelofibrosis (MF) developing in Polycythaemia vera (PV) and Essential Thrombocythemia (ET) shortens patient survival.
- Understanding genetic factors influencing MF progression is crucial for improving outcomes in myeloproliferative neoplasms (MPNs).
Purpose of the Study:
- To investigate the impact of the miR-146a rs2431697 polymorphism on inflammatory biomarkers and gene expression.
- To assess the association between this polymorphism and the risk of myelofibrosis progression in MPN patients.
Main Methods:
- Genotyping of miR-146a rs2431697 in 88 MPN patients (40 PV, 27 ET, 21 MF) and 90 healthy controls using sequencing.
- Quantification of miR-146a, IL-1β, NF-κB, and NLRP3 gene expression via real-time PCR.
- Multivariate analysis to identify predictors of MF progression.
Main Results:
- The TT and TC genotypes of miR-146a rs2431697 were significantly associated with MF.
- MF patients exhibited reduced miR-146a expression and elevated IL-1β, NF-κB, and NLRP3 expression compared to PV and ET patients.
- The TT genotype was identified as a poor predictor of MF progression.
Conclusions:
- The miR-146a rs2431697 TT genotype confers a high risk of MF progression in MPN patients.
- Targeting IL-1β, NF-κB, and NLRP3 pathways presents a potential therapeutic strategy to hinder MF progression.
