Nocturnal Hemoglobinuria

Theories of PNH evolution in the context of AA

The mechanisms of the selective advantage of the PNH clone has been the subject of intense research, but no conclusive results have been obtained. The simplest model to explain how the PIG-A mutation accounts for the ability of the PNH clone to expand predicts that PIG-A mutant cells enjoy an intrinsic growth advantage. Surprisingly, clinical observation and much experimental data do not support this hypothesis.73 Most obviously, PNH does not behave like leukemia. PNH stem cells are capable of producing mature cells of all lineages and respond to many physiologic stimuli. PNH progenitor and stem cells do not accumulate. In same patients, the proportion of PNH cells remains stable for years,70 suggesting that GPI-deficient and normal hematopoiesis may coexist and that PNH cells do not simply displace normal cells. The presence of PNH cells in normal adults is also difficult to reconcile with this model, given the rarity of this disease. The differential susceptibility to apoptosis of PNH cells has been reported by several groups,56,139,140 but their results have not been confirmed by others.141142 Appropriate controls with primary cells are difficult in such experiments, while cell lines may not reflect the situation in vitro.

Clinical features

A PNH clone can be present in a significant proportion of patients with AA at presentation, but most patients harbor small clones without clinical significance. The presence of PNH clones constitutes a positive prognostic factor for the response to immunosuppression. The behavior of the PNH clone in the course of the disease and following therapy is erratic. In some patients, the clonal size does not change, while a clinical PNH can

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