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Updated: Jun 20, 2026
Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
Published on: March 30, 2018
MicroRNA expression, chromosomal alterations, and immunoglobulin variable heavy chain hypermutations in Mantle cell
Alba Navarro1, Sílvia Beà, Verónica Fernández
1Department of Pathology (Hematopathology Unit), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona.
Abstract:
The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known. We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5(+)/CD5(-) normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8 MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization. Leukemic and nodal tumors showed a high number of differentially expressed miRs compared with purified normal B cells, but only some of them were commonly deregulated in both tumor types. An unsupervised analysis of miR expression profile in purified leukemic MCL cells revealed two clusters of tumors characterized by different mutational status of the immunoglobulin genes, proliferation signature, and number of genomic alterations. The expression of most miRs was not related to copy number changes in their respective chromosomal loci. Only the levels of miRs included in the miR-17-92 cluster were significantly related to genetic alterations at 13q31. Moreover, overexpression of miR-17-5p/miR-20a from this cluster was associated with high MYC mRNA levels in tumors with a more aggressive behavior. In conclusion, the miR expression pattern of MCL is deregulated in comparison with normal lymphoid cells and distinguishes two subgroups of tumors with different biological features.
Insights
MicroRNA (miR) expression is altered in mantle cell lymphoma (MCL), a type of non-Hodgkin lymphoma. This deregulation helps distinguish MCL tumor subgroups with distinct biological features.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of microRNAs (miRs) in mantle cell lymphoma (MCL) pathogenesis remains largely uncharacterized.
- MCL is a B-cell lymphoma with specific genetic alterations.
Purpose of the Study:
- To investigate microRNA expression profiles in MCL.
- To correlate miR deregulation with genomic alterations and biological features in MCL.
Main Methods:
- Examined expression of 86 miRs in normal B cells, reactive lymph nodes, and MCL tumors (leukemic, nodal, cell lines).
- Utilized SNP arrays and CGH for genomic alteration analysis.
- Performed unsupervised analysis of miR expression profiles.
Main Results:
- MCL tumors exhibited significant miR deregulation compared to normal B cells.
- Two distinct MCL tumor clusters emerged based on miR expression, linked to mutational status, proliferation, and genomic alterations.
- miR-17-92 cluster alterations correlated with 13q31 genetic changes; miR-17-5p/miR-20a overexpression associated with high MYC mRNA and aggressive behavior.
Conclusions:
- MicroRNA expression patterns are significantly deregulated in MCL.
- miR expression profiling can differentiate MCL subgroups with distinct biological characteristics.
