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T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile

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Abstract

T cells may have a role in sustaining the leukemic clone in chronic lymphocytic leukemia (CLL). In this study, we have examined the ability of T cells from CLL patients to support the survival of the leukemic B cells in vitro. Additionally, we compared global gene expression of T cells from indolent CLL patients with healthy individuals and multiple myeloma (MM) patients. Apoptosis of purified leukemic B cells was inhibited in vitro when co-cultured with increasing numbers of autologous T cells (p < 0.01) but not autologous B and T cells of normal donors. The anti-apoptotic effect exceeded that of the anti-apoptotic cytokine IL-4 (p = 0.002) and was greater with CD8+ cells (p = 0.02) than with CD4+ cells (p = 0.05). The effect was depended mainly on cell–cell contact although a significant effect was also observed in transwell experiments (p = 0.05). About 356 genes involved in different cellular pathways were deregulated in T cells of CLL patients compared to healthy individuals and MM patients. The results of gene expression profiling were verified for 6 genes (CCL4, CCL5 (RANTES), XCL1, XCL2, KLF6, and TRAF1) using qRT–PCR and immunoblotting. Our results demonstrate that CLL-derived T cells can prevent apoptosis of leukemic B cells and have altered expression of genes that may facilitate the survival of the leukemic clone.

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Acknowledgments

This study was supported by grants from The Swedish Cancer Society, The Cancer Society in Stockholm, The King Gustav V Jubilee Fund, The Stockholm County Council, The Cancer and Allergy Foundation, Torsten and Ragnar Söderberg Foundations, The Karolinska Institutet Foundations, and the Ministry of Health and Medical Education of Iran. We thank Ms Leila Relander for excellent secretarial help.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cancer Center Karolinska, Department of Oncology-Pathology (Radiumhemmet), Karolinska University Hospital, Solna, Karolinska Institutet, 171 76, Stockholm, Sweden

    Eva Rossmann, Marzia Palma, Lotta Hansson, Anders Österborg & Håkan Mellstedt

  2. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

    Eva Rossmann, Marzia Palma, Lotta Hansson, Kaveh Mashayekhi & Anders Österborg

  3. Institute of Cancer, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Shahryar Kiaii

  4. Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran

    Parviz Kokhaei & Fatemeh Pak

  5. Center for Immune and Targeted Therapy Greenslopes Private Hospital, Newdegate Street, Brisbane, QLD, 4072, Australia

    Aniruddha Choudhury

  6. Cancer Center Karolinska, Department of Oncology-Pathology (Radiumhemmet), Karolinska Institutet, 171 76, Stockholm, Sweden

    Shahryar Kiaii, Parviz Kokhaei, Fariba Mozaffari, Fatemeh Pak, Ali Moshfegh, Mohammad Hojjat-Farsangi & Aniruddha Choudhury

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  1. Shahryar Kiaii
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  2. Parviz Kokhaei
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Correspondence to Håkan Mellstedt.

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Shahryar Kiaii and Parviz Kokhaei contributed equally to this article.

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Kiaii, S., Kokhaei, P., Mozaffari, F. et al. T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile. Cancer Immunol Immunother 62, 51–63 (2013). https://doi.org/10.1007/s00262-012-1300-y

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