title: Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria.
abstract: Patients with paroxysmal nocturnal haemoglobinuria (PNH) have in their blood two red-cell populations, one normal and one deficient in proteins anchored to the membrane through a glycan phosphatidylinositol (GPI) structure. The PNH abnormality is due to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor biosynthesis. We show that in two patients, two PNH clones with different mutations co-exist, and must therefore have arisen independently. This finding supports the concept that PNH develops under the pressures of a positive selection mechanism whereby GPI-anchor-deficient haemopoietic cells have a survival advantage.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bessler
authors.forename: P
authors.initials: P
authors.lastname: Mason
authors.forename: P
authors.initials: P
authors.lastname: Hillmen
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D002460:Cell Line; D002999:Clone Cells; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols