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Critical Signal Transduction Pathways in CLL | SpringerLink

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Critical Signal Transduction Pathways in CLL

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Advances in Chronic Lymphocytic Leukemia

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Abstract

Receptor tyrosine kinases (RTKs) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play a critical role in signal transduction in both normal and malignant cells. Besides B cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL), multiple RTKs have been reported to be constitutively active in CLL B cells, resulting in enhanced survival and resistance to apoptosis of the leukemic cells induced by chemotherapeutic agents. In addition to increased plasma levels of various types of cytokines/growth factors in CLL, we and others have detected that CLL B cells spontaneously produce multiple cytokines in vitro which may constitute an autocrine loop of RTK activation on the leukemic B cells. Moreover, aberrant expression and activation of non-RTKs, for example, Src/Syk kinases, induce resistance of the leukemic B cells to therapy. Based on current available knowledge, we detailed the impact of aberrant activities of various RTKs/non-RTKs on CLL B cell survival and the potential of using these signaling components as future therapeutic targets in CLL therapy.

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Acknowledgements

Part of the research information on CLL used in this review chapter was generated in our laboratories supported by the NIH research fund CA95241 (to NEK) and Eagles Cancer Research fund (to AKG). We acknowledge Ms. Tammy Hughes for her excellent secretarial help on this chapter.

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  1. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Asish K. Ghosh Ph.D. & Neil E. Kay M.D.

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  1. Asish K. Ghosh Ph.D.
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Correspondence to Neil E. Kay M.D. .

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  1. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Sami Malek

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Ghosh, A.K., Kay, N.E. (2013). Critical Signal Transduction Pathways in CLL. In: Malek, S. (eds) Advances in Chronic Lymphocytic Leukemia. Advances in Experimental Medicine and Biology, vol 792. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8051-8_10

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