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Updated: Sep 3, 2025
A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
Published on: June 16, 2022
MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia
Bo Guo1, Ran Qin2, Ji Jun Chen3
1Department of Hematology, The Second Medical Centre & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China;Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA;Yale Stem Cell Center, Yale Cancer Center, New Haven, CT, 06520, USA.
Objective:
Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.
Methods:
Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.
Results:
MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.
Conclusion:
This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.
Insights
Overexpression of miR-125b accelerates acute promyelocytic leukemia (APL) development. This microRNA is involved in APL
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute promyelocytic leukemia (APL) is often associated with the PML-RARa fusion oncogene.
- APL patients typically present with low peripheral white blood cell counts.
Purpose of the Study:
- To investigate the role of miR-125b overexpression in APL pathogenesis.
- To determine if miR-125b contributes to the characteristic low white cell count in APL.
Main Methods:
- Utilized an inducible mouse model engineered to overexpress human miR-125b.
- Assessed the impact of miR-125b on PML-RARa-induced leukemogenesis.
Main Results:
- miR-125b significantly accelerated PML-RARa-driven leukemogenesis.
- The induced leukemia showed partial dependence on sustained miR-125b overexpression.
- miR-125b expression correlated with a low peripheral white cell count to bone marrow blast percentage ratio, mirroring clinical APL observations.
Conclusions:
- Dysregulated miR-125b expression actively contributes to APL progression and pathophysiology.
- Targeting miR-125b presents a potential novel therapeutic strategy for APL treatment.
