Pathogenesis of Selective Expansion of PNH Clones

Progress in hematology

DOI: 10.1007/BF02983210

Cite this article as:
Nakakuma, H. & Kawaguchi, T. Int J Hematol (2003) 77: 121. doi:10.1007/BF02983210


Hemolysis, a characteristic of paroxysmal nocturnal hemoglobinuria (PNH), is caused by the expansion of an affected stern cell with a mutation of the PIG-A gene. Increasing evidence has shown that the presence of the PIG-A mutation alone does not induce the expansion. Two theories have been proposed. One, the growth advantage hypothesis, is supported by current data indicating the presence of several intrinsic alterations that might confer a proliferative advantage to PNH clones over normal cells. Alternatively, the PIG-A mutation might confer a relative survival advantage to PNH clones. This theory is supported by clinical observation indicating that PIG-A mutant cells survive immune-mediated bone marrow injury in patients with aplastic anemia, PNH, and myelodysplastic syndromes. The latter theory is also supported by current experimental data indicating that PIG-A mutant cells are relatively resistant to cytotoxic attack by natural killer cells and cytotoxic T-lymphocytes. The 2 theories appear complementary rather than mutually exclusive. Rapid progress in this field can be expected in the near future.

Key words

Paroxysmal nocturnal hemoglobinuria Clonal expansion PIG-A Glycosylphosphatidylinositol Natural killer cells 

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  1. 1.Second Department of Internal MedicineKumamoto University School of MedicineKumamotoJapan

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