[Granulopoeisis and leukemogenesis: lessons from congenital neutropenia]

Med Sci (Paris). 2008 Mar;24(3):284-9. doi: 10.1051/medsci/2008243284.
[Article in French]

Abstract

Congenital neutropenia are extremely rare diseases, defined by a permanent or cyclic decrease of blood neutrophils. Molecular basis of several congenital neutropenia has been recently determined, involving gene coding for the neutrophil elastase gene (ELA2), GFI1, WAS protein and mitochondrial HAX1 protein. These mutations, dominant (ELA2, GFI1), X-linked (WAS) and autosomal recessive (HAX1), result in instability of the contents of the granules- particularly the neutrophil elastase- or in abnormalities of the cytoskeleton, and possibly, in an increased apoptosis. ELA2 mutations resulting both in profound and permanent neutropenia, and in cyclic--pseudo sinusoidal--neutropenia lead to consider that time pattern is very close in the two apparently distinct phenotypes. This observation suggests that temporal variations of neutrophils could be represented by non linear functions. Congenital neutropenia, specifically ELA2 mutated, are also characterized by a high rate of leukemia (about 15% at 20 years of age). Leukemia risk does not appear to be related to an oncogenic effect of ELA2 mutations, but much likely to the deepness of the neutropenia, and the intensity of G-CSF therapy.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Cytoplasmic Granules / enzymology
  • Cytoplasmic Granules / ultrastructure
  • Cytoskeleton / ultrastructure
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Leukemia / etiology*
  • Leukemia / physiopathology
  • Leukocyte Elastase / deficiency
  • Leukocyte Elastase / genetics
  • Leukocyte Elastase / physiology
  • Mice
  • Mice, Knockout
  • Myelopoiesis / physiology*
  • Neutropenia / congenital*
  • Neutropenia / drug therapy
  • Neutropenia / genetics
  • Neutropenia / physiopathology
  • Neutrophils / physiology*
  • Nonlinear Dynamics
  • Risk
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Wiskott-Aldrich Syndrome Protein / deficiency
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / physiology

Substances

  • DNA-Binding Proteins
  • GFI1 protein, human
  • Gfi1 protein, mouse
  • Transcription Factors
  • WAS protein, human
  • Wiskott-Aldrich Syndrome Protein
  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Elastase