Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression.
B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, occurs in two forms, aggressive (showing for the most part high ZAP-70 expression and unmutated IgH V(H)) and indolent (showing low ZAP-70 expression and mutated IgH V(H)). We found that miR-29a is up-regulated in indolent human B-CLL as compared with aggressive B-CLL and normal CD19(+) B cells. To study the role of miR-29 in B-CLL, we generated Emu-miR-29 transgenic mice overexpressing miR-29 in mouse B cells. Flow cytometric analysis revealed a markedly expanded CD5(+) population in the spleen of these mice starting at 2 mo of age, with 85% (34/40) of miR-29 transgenic mice exhibiting expanded CD5(+) B-cell populations, a characteristic of B-CLL. On average, 50% of B cells in these transgenic mice were CD5 positive. At 2 y of age the mice showed significantly enlarged spleens and an increase in the CD5(+) B-cell population to approximately 100%. Of 20 Emu-miR-29 transgenic mice followed to 24-26 mo of age, 4 (20%) developed frank leukemia and died of the disease. These results suggest that dysregulation of miR-29 can contribute to the pathogenesis of indolent B-CLL.
Santanam
Urmila
U
Department of Molecular Virology, Ohio State University School of Medicine, Ohio State University, Columbus, OH 43210, USA.
Zanesi
Nicola
N
Efanov
Alexey
A
Costinean
Stefan
S
Palamarchuk
Alexey
A
Hagan
John P
JP
Volinia
Stefano
S
Alder
Hansjuerg
H
Rassenti
Laura
L
Kipps
Thomas
T
Croce
Carlo M
CM
Pekarsky
Yuri
Y
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D018941:Antigens, CD19; D018956:CD5 Antigens; C532045:MIRN29a microRNA, human; D035683:MicroRNAs