Details

Autor(en) / Beteiligte

• Dunn, Daniel E.
• Liu, Johnson M.
• Young, Nael S.

Titel

5 - Bone Marrow Failure in PNH

Ist Teil von

• PNH and the GPI-Linked Proteins, 2000, p.113-137

Ort / Verlag

Academic Press

Erscheinungsjahr

2000

Link zum Volltext

Quelle

ScienceDirect eBooks

Beschreibungen/Notizen

• Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder in which PIG-A mutant clones of hematopoietic stem cells undergo massive but nonneoplastic expansion. The only known consequence of PIG-A gene dysfunction is the loss of glycosylphosphatidylinositol anchored proteins (GPI-AP) expression by the mutant hematopoietic stem cells and its progeny. In erythrocytes, this defect results in episodes of intravascular hemolysis when complement is activated in the context of inflammation; in platelets, the defect is believed to favor thrombus formation. On the other hand, PIG-A mutations do not appear to directly give rise to the bone marrow aplasia that frequently accompanies PNH. Instead, it would seem that the underlying pathophysiologic process of aplastic anemia confers a relative survival advantage to PIG-A mutant stem cells. Clarifying the molecular basis for this “unnatural” selection process will likely impact the understanding not only of PNH, AA, and other autoimmune syndromes, but also of the unique biology of GPI-AP as well as the adaptive physiology of hematopoietic stem cells.