| Abstract: | To test the hypothesis that paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder, the growth of BFU-e and CFU-gm and the complement sensitivity of cultured cells from BFU-e and CFU-gm colonies, as well as of unipotential progenitor cells (CFU-gm and BFU-e), were examined in five PNH patients. BFU-e growth was reduced in the three patients examined, and poor CFU-gm growth was noted in three of the five patients. Compared to normals, BFU-e and CFU-gm colonies in all patients demonstrated an increased susceptibility to the lytic action of complement when the release of 59Fe and myeloperoxidase was measured as specific markers for monitoring membrane damage. Compared to the growth of normal bone marrow cells, CFU-gm growth was significantly inhibited by pretreatment of bone marrow mononuclear cells with monoclonal OKIal antibody and complement. These findings support the proposition that a membrane defect predisposing blood cells to complement-mediated lysis may occur at the level of unipotential progenitor cells. |
