1. T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile.
- Author
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Kiaii S, Kokhaei P, Mozaffari F, Rossmann E, Pak F, Moshfegh A, Palma M, Hansson L, Mashayekhi K, Hojjat-Farsangi M, Österborg A, Choudhury A, and Mellstedt H
- Subjects
- Aged, Aged, 80 and over, Coculture Techniques, Female, Flow Cytometry, Humans, Immunoblotting, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Middle Aged, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Apoptosis immunology, B-Lymphocytes immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, T-Lymphocytes immunology, Transcriptome
- 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.
- Published
- 2013
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