Heterogeneity in the molecular pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH) syndromes and expansion mechanism of a PNH clone.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder that is manifested by complement-mediated hemolysis, venous thrombosis, and bone marrow failure and is one disorder of acquired bone marrow failure syndromes that include as aplastic anemia and myelodysplastic syndrome. Nowadays, acquired PNH should be understood as one of the disorders of PNH syndromes. These syndromes include congenital PNH (such as inherited complete CD59 deficiency and PNH with PIG-M mutations), because complement-mediated hemolysis and thrombosis are observed in association with defects of various factors associated with the complement regulatory pathway, including biosynthesis of the glycosylphosphatidylinositol (GPI) anchor. At present, how a "true" PNH clone in acquired PNH expands in the bone marrow remains unclear. Although several candidate genes, including the Wilms tumor gene, the early growth response gene, anti-apoptotic genes, and the high mobility group AT-hook 2 gene, that target corresponding proteins (excluding GPI-related proteins) have been reported, the evidence is insufficient to completely explain the diversity of the clinical and basic pathophysiology in acquired PNH. However, the hypothesis of expansion of a PNH clone due to the WT1 gene may explain various features of PNH.
Shichishima
Tsutomu
T
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan. t-shichi@fmu.ac.jp
Noji
Hideyoshi
H
D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003167:Complement Activation / Q000235:genetics; D005786:Gene Expression Regulation; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006461:Hemolysis / Q000235:genetics; D006801:Humans; D009154:Mutation; D013577:Syndrome; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology