Critical signal transduction pathways in CLL

Asish K. Ghosh, Neil E. Kay

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations

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 Chronic Lymphocytic Leukemia
PublisherSpringer New York LLC
Pages215-239
Number of pages25
ISBN (Print)9781461480501
DOIs
StatePublished - 2013

Publication series

NameAdvances in Experimental Medicine and Biology
Volume792
ISSN (Print)0065-2598

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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