CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation

Leukemia. 2010 May;24(5):970-5. doi: 10.1038/leu.2010.46. Epub 2010 Apr 1.


B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia. Deregulation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene in mouse B cells causes a CD5-positive leukemia similar to aggressive human B-CLLs. We recently reported that levels of TCL1 expression in B-CLL are regulated by miR-29 and miR-181 that target 3' UTR of TCL1. To determine whether treatment with microRNAs targeting TCL1 can inhibit B-CLL in mice, we generated TCL1 transgenic mice using a construct containing the 3' and 5' UTRs of TCL1 under B-cell-specific Emicro promoter (Emicro-TCL1FL). At the age of 16-20 months, these mice showed B-CLL-like disease. Immunophenotyping revealed accumulation of CD5+CD23+B220+ population in spleens and lymph nodes. Our results show that CD5+CD23+ B-cell populations from Emicro-TCL1FL mice actively proliferate and show significantly increased levels of phospho-Akt. Emicro-TCL1FL mice showed immunological abnormalities similar to human B-CLL, including hypoimmunoglobulinemia, abnormal levels of cytokines and impaired immune response. These findings revealed biochemical and immunological similarities between Tcl1-driven B-CLL in mice and human B-CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 5' Untranslated Regions / genetics
  • Animals
  • Blotting, Western
  • CD5 Antigens / metabolism*
  • Cell Proliferation*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunization
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Transgenic
  • MicroRNAs / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgE / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / metabolism
  • Spleen / pathology


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • CD5 Antigens
  • Cd5 protein, mouse
  • Cytokines
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, IgE
  • TCL1A protein, human
  • Proto-Oncogene Proteins c-akt