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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.
AuthorsT Shichishima, T Terasawa, C Hashimoto, H Ohto, M Takahashi, A Shibata, Y Maruyama
JournalBlood (Blood) Vol. 81 Issue 7 Pg. 1855-62 (Apr 1 1993) ISSN: 0006-4971 [Print] UNITED STATES
PMID7681703 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Antigens, CD55
  • Antigens, CD58
  • Antigens, CD59
  • Glycosylphosphatidylinositols
  • Membrane Glycoproteins
  • Proteins
  • Receptors, IgG
  • Phosphoric Diester Hydrolases
  • Phosphoinositide Phospholipase C
  • Phosphatidylinositol Diacylglycerol-Lyase
Topics
  • Antigens, CD (blood, drug effects)
  • Antigens, CD55
  • Antigens, CD58
  • Antigens, CD59
  • Glycosylphosphatidylinositols (blood)
  • Hemoglobinuria, Paroxysmal (blood, enzymology, pathology)
  • Hemolysis
  • Humans
  • Leukemia, Myeloid, Acute (blood, enzymology, pathology)
  • Male
  • Membrane Glycoproteins (blood, drug effects)
  • Middle Aged
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Phosphoinositide Phospholipase C
  • Phosphoric Diester Hydrolases (pharmacology)
  • Proteins (metabolism)
  • Receptors, IgG (metabolism)

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