Bessler M, Mason P, Hillmen P, Luzzatto L
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Lancet. 1994 Apr 16;343(8903):951-3. doi: 10.1016/s0140-6736(94)90068-x.
Patients with paroxysmal nocturnal haemoglobinuria (PNH) have in their blood two red-cell populations, one normal and one deficient in proteins anchored to the membrane through a glycan phosphatidylinositol (GPI) structure. The PNH abnormality is due to a somatic mutation in the PIG-A gene, whose product is required for an early step in GPI anchor biosynthesis. We show that in two patients, two PNH clones with different mutations co-exist, and must therefore have arisen independently. This finding supports the concept that PNH develops under the pressures of a positive selection mechanism whereby GPI-anchor-deficient haemopoietic cells have a survival advantage.
阵发性夜间血红蛋白尿（PNH）患者的血液中有两种红细胞群体，一种正常，另一种缺乏通过糖基磷脂酰肌醇（GPI）结构锚定在膜上的蛋白质。PNH异常是由于PIG-A基因的体细胞突变，该基因的产物是GPI锚生物合成早期步骤所必需的。我们发现，在两名患者中，两个具有不同突变的PNH克隆共存，因此必定是独立产生的。这一发现支持了以下概念：PNH是在正选择机制的压力下发展而来的，即GPI锚缺陷的造血细胞具有生存优势。
