Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice.

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.

• Authors: Stefan Costinean, Nicola Zanesi, Yuri Pekarsky, Esmerina Tili, Stefano Volinia, Nyla Heerema, Carlo M Croce
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 18 Pg. 7024-9 (May 02 2006) ISSN: 0027-8424 [Print] United States
• PMID: 16641092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Surface
• Immunoglobulin Heavy Chains
• Immunoglobulin M
• MicroRNAs

Topics

• Animals
• Antigens, Surface (genetics, metabolism)
• B-Lymphocytes (cytology, physiology)
• Body Weight
• Bone Marrow Cells (physiology)
• Cell Proliferation
• Chromosome Aberrations
• Cytogenetics
• Humans
• Immunoglobulin Heavy Chains (genetics, metabolism)
• Immunoglobulin M (metabolism)
• Leukemia, Lymphoid (genetics, immunology)
• Lymphoma, Non-Hodgkin (genetics, immunology)
• Mice
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Organ Size
• Spleen (cytology, pathology)
• Transgenes