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Surface membrane antigen expression changes induced in vitro by exogenous growth factors in chronic lymphocytic leukemia cells

Leukemia volume 16, pages 1691–1698 (2002)Cite this article

Abstract

The factors determining the growth and survival of cells in B chronic lymphocytic leukemia (CLL) have remained poorly understood. We investigated the effects of optimal mitogen combinations (OMCs) on the expression of 26 surface membrane antigens among 33 CLL patients. The seven OMCs used were selected after pre-testing 14 combinations of (1) S. aureus Cowan I (SAC), (2) interleukin-2 (IL-2), (3) tumor necrosis factor alpha (TNF-α) and (4) 12-O-tetradecanoylphorbol 13-acetate (TPA; also known as phorbol 12-myristate 13-acetate or PMA). In flow cytometry we revealed that OMCs induced statistically highly significant upregulation of the expression of CD5, CD11c, CD19, CD22, CD23, CD25, CD38, CD40, CD45, CD45RO, CD95, CD126, CD130 and FMC7, and downregulation of CD20 and CD124 expression. Interestingly, the expression of CD27, CD45RA, CD79b, CD80, CD122 and that of the immunoglobulin gene superfamily members CD21, Ig-κ, Ig-λ, Ig-δ and Ig-μ were not significantly affected under similar conditions. The expression of several antigens was co-regulated, suggesting common regulatory pathways. These antigens include CD11c/CD5, CD11c/CD22, CD11c/CD126, CD11c/FMC7 as well as CD27/CD45, CD27/CD45RA and CD27/CD79b. Upregulation of surface antigen expression, induced by OMCs, should be applicable in antibody therapy in vitro and in vivo, and in negative stem cell selection for autotransplantation. Furthermore, the current strategy to enhance cell surface antigen expression may be a versatile tool to raise humoral and cell-mediated host defense against CLL cells. Upregulation of proteins mediating positive growth signals (eg CD25, CD40) and negative signals or apoptosis (eg CD95) may be used to sensitize cells to chemotherapy and programmed cell death.

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Acknowledgements

We thank Leena Pankko and Merja Suoranta for their technical assistance. This work was supported by grants from the Medical Research Fund of Tampere University Hospital, and the Finnish Cancer Organization.

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  1. Department of Clinical Chemistry, University of Tampere Medical School and Laboratory Centre of Tampere University Hospital, Tampere, Finland

    J Vilpo & L Vilpo

  2. Department of Microbiology and Immunology, University of Tampere, Medical School and Laboratory Centre of Tampere University Hospital, Tampere, Finland

    J Hulkkonen & M Hurme

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Vilpo, J., Hulkkonen, J., Hurme, M. et al. Surface membrane antigen expression changes induced in vitro by exogenous growth factors in chronic lymphocytic leukemia cells. Leukemia 16, 1691–1698 (2002). https://doi.org/10.1038/sj.leu.2402583

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