Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure

Br J Haematol. 2009 Oct;147(1):102-12. doi: 10.1111/j.1365-2141.2009.07822.x. Epub 2009 Jul 28.

Abstract

Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Aplastic / blood
  • Anemia, Aplastic / genetics
  • Follow-Up Studies
  • Glycosylphosphatidylinositols / blood
  • Glycosylphosphatidylinositols / deficiency*
  • Granulocytes / metabolism
  • Hemoglobinuria, Paroxysmal / blood*
  • Hemoglobinuria, Paroxysmal / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / genetics

Substances

  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • phosphatidylinositol glycan-class A protein