title: Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria.
abstract: We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF-positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical College, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shichishima
authors.forename: T
authors.initials: T
authors.lastname: Terasawa
authors.forename: C
authors.initials: C
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Ohto
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000187:drug effects; D018958:CD55 Antigens; D018968:CD58 Antigens; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols / Q000097:blood*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D006461:Hemolysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000187:drug effects; D008875:Middle Aged; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018958:CD55 Antigens; D018968:CD58 Antigens; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D011506:Proteins; D017452:Receptors, IgG; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase