Rho and Rap guanosine triphosphatase signaling in B cells and chronic lymphocytic leukemia

Silvia Mele, Stephen Devereux, Anne J Ridley

Research output: Contribution to journalReview article (Academic Journal)peer-review

Abstract

Chronic lymphocytic leukemia (CLL) cells proliferate predominantly in niches in the lymph nodes, where signaling from the B cell receptor (BCR) and the surrounding microenvironment are critical for disease progression. In addition, leukemic cells traffic constantly from the bloodstream into the lymph nodes, migrate within lymphatic tissues and egress back to the bloodstream. These processes are driven by chemokines and their receptors, and depend on changes in cell migration and integrin-mediated adhesion. Here we describe how Rho and Rap guanosine triphosphatases (GTPases) contribute to both BCR signaling and chemokine receptor signaling, particularly by regulating cytoskeletal dynamics and integrin activity. We propose that new inhibitors of BCR-activated kinases are likely to affect CLL cell trafficking via Rho and Rap GTPases, and that upstream regulators or downstream effectors could be good targets for therapeutic intervention in CLL.

Original languageEnglish
Pages (from-to)1993-2001
Number of pages9
JournalLeukemia and Lymphoma
Volume55
Issue number9
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Animals
  • B-Lymphocytes
  • Cell Movement
  • Cell Proliferation
  • Chemokines
  • Cytoskeleton
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoid Tissue
  • Molecular Targeted Therapy
  • Receptors, Antigen, B-Cell
  • Signal Transduction
  • rap GTP-Binding Proteins
  • rho GTP-Binding Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

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