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Up-regulation of MicroRNA 146b is Associated with Myelofibrosis in Myeloproliferative Neoplasms
1Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu ksksmom@naver.com ksksmom@dsmc.or.kr.
Abstract:
In this study, our goal was to evaluate whether the expressions of microRNA (miR)-150, miR-146b, miR-31 and miR-95 demonstrate primary myelofibrosis (PMF) specificity, associations with fibrosis grade, hematologic phenotypes, or myeloproliferative neoplasm (MPN)-associated mutations. A total of 51 formalin-fixed and paraffin-embedded bone marrow MPN samples, including 15 polycythemia vera (PV), 26 essential thrombocythemia (ET), and 10 PMF, and 24 normal controls were included. The expression of microRNA (miRNA) was detected by quantitative real-time polymerase chain reaction using miRNA specific primers. RNU6-2 was analyzed for all samples as endogenous control for relative quantification. Information for fibrosis, hematologic parameters, Janus kinase 2 (JAK2) V617F, and calreticulin (CALR) mutations was obtained from medical records. Significant increment of miR-146b was detected in PMF compared to normal controls (P=0.008). Moreover, expression of miR-146b tended to increase according to increment of fibrosis grade, and patients with myelofibrosis (MF) grade 3 showed significantly higher expression than patients with MF 0 to 2 (P=0.022, 0.001 and 0.013, respectively) or normal controls (P<0.001). The expression of miR-31 also showed tendency to increase following fibrosis and miR-150 showed up-regulated expression in ET (P=0.015) compared to normal control. There was no relationship between miRNA expression and hematologic indices except miR-95 showed negative correlation with platelet count (P=0.024). There was no significant correlation between miRNA expression and JAK2 V617F or CALR mutation. Up-regulation of miR-146b could be used as a fibrosis-indicating marker and might be helpful in the study of fibrotic mechanism in MPN, as well as other fibrotic diseases.
Insights
MicroRNA-146b expression is elevated in primary myelofibrosis (PMF) and correlates with fibrosis severity, suggesting its potential as a fibrosis marker in myeloproliferative neoplasms (MPNs).
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Myeloproliferative neoplasms (MPNs) are a group of blood cancers characterized by the overproduction of myeloid cells.
- Primary myelofibrosis (PMF) is an MPN associated with significant bone marrow fibrosis, impacting hematopoiesis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases, including cancers.
Purpose of the Study:
- To investigate the specificity of miR-150, miR-146b, miR-31, and miR-95 expression in primary myelofibrosis (PMF).
- To assess the association of these miRNA expressions with fibrosis grade, hematologic phenotypes, and common MPN mutations (JAK2, CALR).
- To determine the potential of specific miRNAs as diagnostic or prognostic markers in MPNs.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure miRNA expression levels.
- The study included 51 bone marrow samples from MPN patients (PV, ET, PMF) and 24 normal controls.
- Fibrosis grade, hematologic parameters, and JAK2 V617F/CALR mutation status were analyzed alongside miRNA expression.
Main Results:
- miR-146b expression was significantly higher in PMF patients compared to normal controls and showed a positive correlation with fibrosis grade.
- Patients with grade 3 myelofibrosis exhibited significantly higher miR-146b expression than those with lower grades or normal controls.
- miR-31 expression tended to increase with fibrosis, miR-150 was upregulated in essential thrombocythemia (ET), and miR-95 negatively correlated with platelet count.
Conclusions:
- Up-regulation of miR-146b may serve as a fibrosis-indicating biomarker in PMF and other myeloproliferative neoplasms.
- miR-146b's role in fibrotic mechanisms warrants further investigation in MPNs and other fibrotic conditions.
- No significant correlation was found between the studied miRNA expressions and JAK2 or CALR mutations.
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