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Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells

Leukemia volume 16, pages 2429–2437 (2002)Cite this article

Abstract

We used oligonucleotide microarrays to profile the expression of chronic lymphocytic leukemia (CLL) B cells from eight patients compared with CD5-expressing normal B cells from four donors and with pooled normal circulating B cells. Of 6790 genes examined, we identified 87 genes that were differentially expressed at least two-fold between CLL and the normal B cells. CLL cells significantly down-regulated transcripts from CD1c and CD1d genes, which encode proteins known to present lipid antigen and mediate innate and adaptive immunity. The expression pattern was also consistent with reduced signaling by interferon gamma but increased response to interleukin 4 in leukemic cells. CLL cells increased the expression of several collagen-associated extracellular matrix and adhesion molecules, up-regulated many genes involved in intracellular protein transport and processing, while downregulating genes involved in proliferation and metabolism. Based on the expression pattern, we propose that CLL-B cells prolong their survival through increased interaction with survival factors such as IL-4, and through various mechanisms of evading the immune response, such as turning off the expression of CD1c and CD1d, reducing immunogenic response to interferon gamma, inactivating T cell in B–T interaction and increasing the expression of immunoglobulin receptors which neutralize antibody-dependent cell-mediated cytotoxicity.

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Acknowledgements

We are grateful to Lenn Flechter for help with clinical samples. The GeneChip array hybridizations were performed in the Affymetrix Academic User Center. The authors acknowledge the support of NIH grants 5R01CA056764-08 and P01HG01323 for this work.

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Author notes

  1. CA Harrington

    Present address: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97006, USA

Authors and Affiliations

  1. Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA

    Z Zheng

  2. Affymetrix, Inc, Santa Clara, CA, USA

    S Venkatapathy, G Rao & CA Harrington

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  1. Z Zheng
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  2. S Venkatapathy
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Correspondence to Z Zheng.

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Zheng, Z., Venkatapathy, S., Rao, G. et al. Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia 16, 2429–2437 (2002). https://doi.org/10.1038/sj.leu.2402711

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