Granulocyte colony-stimulating factor receptor signaling: implications for G-CSF responses and leukemic progression in severe congenital neutropenia

Hematol Oncol Clin North Am. 2013 Feb;27(1):61-73, viii. doi: 10.1016/j.hoc.2012.10.002. Epub 2012 Oct 31.

Abstract

Following activation by their cognate ligands, cytokine receptors undergo intracellular routing toward lysosomes, where they are degraded. This review focuses on the signaling function of the G-CSFR in relation to the dynamics of endosomal routing of the G-CSFR. Mechanisms involving receptor lysine ubiquitination and redox-controlled phosphatase activities are discussed. Specific attention is paid to the consequences of G-CSFR mutations, acquired in patients with severe congenital neutropenias who receive G-CSF therapy, particularly in the context of leukemic transformation, a major clinical complication of the disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism
  • Congenital Bone Marrow Failure Syndromes
  • Disease Progression
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Leukemia / etiology
  • Lysosomes / metabolism
  • Mutation
  • Neutropenia / congenital*
  • Neutropenia / drug therapy
  • Neutropenia / genetics
  • Neutropenia / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Granulocyte Colony-Stimulating Factor / deficiency
  • Receptors, Granulocyte Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte Colony-Stimulating Factor / metabolism*
  • Signal Transduction*
  • Ubiquitination

Substances

  • Reactive Oxygen Species
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Granulocyte Colony-Stimulating Factor
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3