Critical signal transduction pathways in CLL

Asish K. Ghosh, Neil E. Kay

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
Pages215-239
Number of pages25
Volume792
DOIs
StatePublished - 2013

Publication series

NameAdvances in Experimental Medicine and Biology
Volume792
ISSN (Print)00652598

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Keywords

  • Apoptosis
  • CLL
  • Kinase inhibitor
  • Non-RTK
  • RTK
  • Signal transduction
  • Therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ghosh, A. K., & Kay, N. E. (2013). Critical signal transduction pathways in CLL. In Advances in Experimental Medicine and Biology (Vol. 792, pp. 215-239). (Advances in Experimental Medicine and Biology; Vol. 792). https://doi.org/10.1007/978-1-4614-8051-8-10