Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria

Br J Haematol. 2012 Feb;156(3):383-7. doi: 10.1111/j.1365-2141.2011.08914.x. Epub 2011 Oct 24.

Abstract

Patients with paroxysmal nocturnal haemoglobinuria (PNH) have expanded clonal cells bearing a somatic mutation in the PIGA gene. Our previous study on two PNH patients with chromosome 12 rearrangements demonstrated the involvement of HMGA2 expression in clonal expansion. The present study investigated HMGA2 expression in PNH patients without chromosomal abnormalities. The expression of short HMGA2 with latent exon was significantly high in peripheral blood cells from 18 of 24 patients. Over-expression of truncated HMGA2 in mouse bone marrow cells caused expansion in recipient mice. These results support the idea that deregulated expression of HMGA2 causes expansion of PNH cells.

Publication types

  • Comparative Study

MeSH terms

  • Alternative Splicing
  • Anemia, Aplastic / pathology
  • Animals
  • Bone Marrow Cells / pathology
  • Cell Division
  • Cells, Cultured / transplantation
  • Clone Cells / pathology
  • Colony-Forming Units Assay
  • Exons / genetics
  • Gene Expression Regulation
  • HMGA2 Protein / biosynthesis
  • HMGA2 Protein / genetics
  • HMGA2 Protein / physiology*
  • Hemoglobinuria, Paroxysmal / genetics
  • Hemoglobinuria, Paroxysmal / metabolism*
  • Hemoglobinuria, Paroxysmal / pathology
  • Humans
  • Membrane Proteins / deficiency
  • Mice
  • Radiation Chimera
  • Recombinant Fusion Proteins / physiology
  • Transduction, Genetic

Substances

  • HMGA2 Protein
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • phosphatidylinositol glycan-class A protein