Nature of PNH clones in aplastic anemia

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal, hemolytic disorder characterized by the presence of peripheral blood cells which are deficient in glycosylphosphatidylinositol anchored proteins (GPI - AP). Somatic mutation of the PIG - A gene in a hematopoietic stem cell is responsible for the origin of PNE clone. So far, it is unclear how the mutant stem cell clone dominates hematopoiesis. PNE is closely related to and frequently occurs following aplastic anemia. Our recent study indicated deficient hematopoiesis in vitro in patients with PNH. It is likely that a process inducing bone marrow failure is also responsible for the selection of GPI - AP deficient cells. In order to explore the growth characteristics of PNH clones, we performed regular, repeated flow cytometric analyses of CD59 expression on peripheral blood cells from 32 patients with aplastic anemia. The duration and median time of follow - up were 12-48 and. 20 months, respectively. Twenty - two patients (69%) had one or more occurrences of GPI - AP deficient granulocytes, six of them with PNH erythrocytes on the same occasion. Repeated occurrences of PNH cells (up to four times) were observed in 15 patients (47%). Most of the emerging PNE clones were transient and variable in size. Persistence and expansion of the GPI -. AP deficient populations to the level of clinical PNH were seen in only four patients (12.5%). As the PNH evolved, GPI - AP deficient granulocytes were more apparent than PNH erythrocytes. Our study indicates that PIG - A mutations of hematopoietic stem cells are relatively common among aplastic anemia patients. Our data argue against the concept of an intrinsic growth advantage of PNH clone, on the contrary they support the hypothesis of a selective process which must be persistently strong enough to favor the outgrowth of a GPI - AP deficient population for the evolution of clinical PNH.