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Chronic Lymphocytic Leukemia

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

Leukemia volume 24, pages 970–975 (2010)Cite this article

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Abstract

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 Eμ promoter (Eμ-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 Eμ-TCL1FL mice actively proliferate and show significantly increased levels of phospho-Akt. Eμ-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.

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Acknowledgements

The research was supported by an ACS Research Scholar grant (Y Pekarsky).

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Authors and Affiliations

  1. Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program and Comprehensive Cancer Center, OSU School of Medicine, Ohio State University, Columbus, OH, USA

    A Efanov, N Zanesi, N Nazaryan, U Santanam, A Palamarchuk, C M Croce & Y Pekarsky

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  1. A Efanov
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  2. N Zanesi
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Correspondence to Y Pekarsky.

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Efanov, A., Zanesi, N., Nazaryan, N. et al. CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation. Leukemia 24, 970–975 (2010). https://doi.org/10.1038/leu.2010.46

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