T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile |
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Authors: | Shahryar Kiaii Parviz Kokhaei Fariba Mozaffari Eva Rossmann Fatemeh Pak Ali Moshfegh Marzia Palma Lotta Hansson Kaveh Mashayekhi Mohammad Hojjat-Farsangi Anders Österborg Aniruddha Choudhury Håkan Mellstedt |
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Affiliation: | 3. Institute of Cancer, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK 6. Cancer Center Karolinska, Department of Oncology-Pathology (Radiumhemmet), Karolinska Institutet, 171 76, Stockholm, Sweden 4. Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran 1. Cancer Center Karolinska, Department of Oncology-Pathology (Radiumhemmet), Karolinska University Hospital, Solna, Karolinska Institutet, 171 76, Stockholm, Sweden 2. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden 5. Center for Immune and Targeted Therapy Greenslopes Private Hospital, Newdegate Street, Brisbane, QLD, 4072, Australia
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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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