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Cell cycle effects of IL-10 on malignant B-1 cells

Genes & Immunity volume 2, pages 239–247 (2001)Cite this article

Abstract

IL-10 is overexpressed in human chronic lymphocytic leukemia (CLL), and is an autocrine growth factor involved in the development of malignant B1 clones in NZB mice, a murine model for CLL. Antisense IL-10 oligonucleotide treatment induces apoptosis and cell cycle disruption in these cells both in vitro and in vivo. In addition, NZB IL-10 knock-out mice fail to develop the B-1 clones. Dampening of IL-10 protein production via antisense IL-10 oligonucleotide treatment is correlated with decreased p27/Kip1 protein expression which results in increased cyclin D2, cyclin E and cyclin A associated kinase activity. The action of the antisense oligonucleotides is through alterations in cell cycle regulation, resulting in accelerated cell cycle progression, a G2/M block which culminates in apoptosis induction in the malignant cells. This implies that the role of IL-10 as an autocrine growth factor in malignant B-1 cells lies in its ability to inhibit apoptosis induction through the maintenance of sustainable cell cycle progression in malignant cells.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, NJ, USA

    S Yen Chong, Y-C Lin, F Coffman & E Raveche

  2. Department of Microbiology, University of Pennsylvania, PA, USA

    J Czarneski

  3. Harvard Medical School, Center for Blood Research, USA

    M Zhang

  4. Department of Biochemistry and Molecular Biology, George Washington Med School, WA, USA

    F Kashanchi

Authors
  1. S Yen Chong
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  2. Y-C Lin
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  7. E Raveche
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Correspondence to E Raveche.

Additional information

This work was supported by a grant from the National Institute of Health CA71478 (ER) and a UMDNJ graduate student stipend (SYC). This work is in partial fulfillment of the Ph.D. requirement for SYC

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Yen Chong, S., Lin, YC., Czarneski, J. et al. Cell cycle effects of IL-10 on malignant B-1 cells . Genes Immun 2, 239–247 (2001). https://doi.org/10.1038/sj.gene.6363773

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