Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice.
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.
Costinean
Stefan
S
Comprehensive Cancer Center, Ohio State University, 400 West 12th Avenue, Columbus, OH 43210, USA.
Zanesi
Nicola
N
Pekarsky
Yuri
Y
Tili
Esmerina
E
Volinia
Stefano
S
Heerema
Nyla
N
Croce
Carlo M
CM
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001835:Body Weight; D001854:Bone Marrow Cells / Q000502:physiology; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D003582:Cytogenetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D013154:Spleen / Q000166:cytology / Q000473:pathology; D019076:Transgenes
D000954:Antigens, Surface; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D035683:MicroRNAs