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Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice
Stefan Costinean1, Nicola Zanesi, Yuri Pekarsky
1Comprehensive Cancer Center, Ohio State University, 400 West 12th Avenue, Columbus, OH 43210, USA.
Abstract:
MicroRNAs (miRNAs) represent a newly discovered class of posttranscriptional regulatory noncoding small RNAs that bind to targeted mRNAs and either block their translation or initiate their degradation. miRNA profiling of hematopoietic lineages in humans and mice showed that some miRNAs are differentially expressed during hematopoietic development, suggesting a role in hematopoietic cell differentiation. In addition, recent studies suggest the involvement of miRNAs in the initiation and progression of cancer. miR155 and BIC, its host gene, have been reported to accumulate in human B cell lymphomas, especially in diffuse large B cell lymphomas, Hodgkin lymphomas, and certain types of Burkitt lymphomas. Here, we show that E(mu)-mmu-miR155 transgenic mice exhibit initially a preleukemic pre-B cell proliferation evident in spleen and bone marrow, followed by frank B cell malignancy. These findings indicate that the role of miR155 is to induce polyclonal expansion, favoring the capture of secondary genetic changes for full transformation.
Insights
MicroRNA 155 (miR155) promotes B cell proliferation and malignancy in mice. Overexpression of miR155 leads to preleukemic expansion, ultimately causing B cell lymphoma.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression posttranscriptionally.
- Aberrant miRNA expression is implicated in cancer development, including B cell lymphomas.
- miR155 and its host gene BIC are found in human B cell lymphomas.
Purpose of the Study:
- To investigate the role of miR155 in B cell development and lymphomagenesis.
- To determine if miR155 can induce B cell malignancy in a mouse model.
Main Methods:
- Generation of E(mu)-mmu-miR155 transgenic mice.
- Analysis of hematopoietic cell proliferation in spleen and bone marrow.
- Monitoring for the development of B cell malignancies.
Main Results:
- Transgenic mice exhibited preleukemic pre-B cell proliferation in spleen and bone marrow.
- Mice developed frank B cell malignancy.
- miR155 induced polyclonal expansion, facilitating secondary genetic alterations for transformation.
Conclusions:
- miR155 plays a critical role in inducing B cell proliferation and promoting lymphomagenesis.
- miR155 acts by inducing polyclonal expansion, creating a permissive environment for malignant transformation.
- These findings highlight miR155 as a key oncogenic factor in B cell lymphomas.
