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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.

Pubmed ID: 20566844

Authors

  • Santanam U
  • Zanesi N
  • Efanov A
  • Costinean S
  • Palamarchuk A
  • Hagan JP
  • Volinia S
  • Alder H
  • Rassenti L
  • Kipps T
  • Croce CM
  • Pekarsky Y

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 6, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: P01-CA81534

Mesh Terms

  • Animals
  • Antigens, CD19
  • Antigens, CD5
  • B-Lymphocytes
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression Regulation, Leukemic
  • Humans
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphocyte Count
  • Mice
  • Mice, Transgenic
  • MicroRNAs
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen