Paroxysmal nocturnal hemoglobinuria: correction of abnormal phenotype by somatic cell hybridization.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disorder thought to result from a somatic mutation in a hemopoietic stem cell. PNH may evolve to aplastic anemia or to acute leukemia. PNH cells are deficient in proteins attached to the cell membrane via a glycosylphosphatidylinositol structure, called the GPI anchor, and the primary lesion in PNH is thought to be a defect in the biosynthesis of the GPI anchor. We have recently established permanent lymphoblastoid cell lines that have the PNH phenotype and we report now the isolation of human-human somatic cell hybrid clones obtained by fusing them with normal lymphoblastoid cells. In all of 21 hybrid clones, obtained from five different patients, the expression of three different GPI-linked proteins on the hybrid cells was normal. These findings indicate that the PNH mutant gene is recessive with respect to the normal allele and that a recessive mutation can cause a clonal preneoplastic disorder.
Hillmen
P
P
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Bessler
M
M
Bungey
J
J
Luzzatto
L
L
D015139:Blotting, Southern; D002240:Carbohydrate Sequence; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D005808:Genes, Recessive; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype