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Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells
Güllü Görgün, … , Donna Neuberg, John G. Gribben
Güllü Görgün, … , Donna Neuberg, John G. Gribben
Published July 1, 2005
Citation Information: J Clin Invest. 2005;115(7):1797-1805. https://doi.org/10.1172/JCI24176.
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Research Article Immunology

Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells

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Abstract

To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity.

Authors

Güllü Görgün, Tobias A.W. Holderried, David Zahrieh, Donna Neuberg, John G. Gribben

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Figure 1

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Differentially expressed genes in CD4 cells from patients with CLL compa...
Differentially expressed genes in CD4 cells from patients with CLL compared with healthy donors. Dendrogram of differentially expressed genes by supervised analysis (P < 0.05). (A) CD4 cells from patients with CLL compared with healthy donors. Twenty-two genes were significantly increased (red) and 68 genes significantly decreased (blue) in CD4 cells from CLL patients. (B) Genes involved in Ras-dependent JNK and p38 MAPK pathways in CD4 cells. The dendrogram represents selected genes from A.

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