Somatic Mutations in Paroxysmal Nocturnal Hemoglobinuria: A Blessing in Disguise?

potent hematopoietic stem cell. In support of this notion, the PNH red cells of women heterozygous for two elec-*Permanent address: Division of Hematology trophoretically distinguishable alleles of the X-linked gene encoding glucose 6-phosphate dehydrogenase Federico II University Medical School Via S Pansini 5 were found all to express the same allele, indicating that they belonged to one clone (Oni et al., 1970). Subse-80100 Napoli Italy quently, extensive characterisation of the abnormal cells—which we will refer to for brevity as PNH cells— revealed that several membrane proteins were deficient (Davitz et al., 1986), including CD55 (which inhibits the Names given by physicians to human ailments range formation of or destabilizes the C3 convertase), and from the esoteric to the simplistic, and they may provoke CD59 (which protects the membrane from attack by in the non-physicians anything from intimidation to in-the C5–C9 complex of activated C). While this finding credulity, but probably very few are as picturesque provided a gratifying explanation for the hypersuscepti-as paroxysmal nocturnal hemoglobinuria. In addition, bility to C of PNH red cells (Davitz et al., 1986; see other whereas medical terms do not always adhere to the references in Kinoshita et al., 1995), several puzzling meaning that words have in plain English (a " benign " questions emerged. First, the presence of multiple tumor can kill if it is in the brain, while " pernicious " abnormalities seemed to be in conflict with the notion anemia can be quickly reversed by one shot of vitamin of a single somatic mutation. Second, if a single mutation B12), the phrase paroxysmal nocturnal hemoglobinuria gives the PNH phenotype, it is by definition a dominant (PNH) describes very accurately the telltale sign of this mutation. This would not seem in keeping with a defect condition. Indeed, the patient may be a child or an old-in a biosynthetic enzyme, since nearly all enzyme defi-age pensioner, a male or a female, may be from any ciencies are recessive. Third, if the mutated clone ex-part of the world, and may have been always well, until pands to the point of accounting for a substantial pro-she or he wakes up one morning to the rather unpleasant portion of hematopoiesis (usually ‫%05ف‬ and often surprise that the urine has turned intensely dark, as more), it must mean that at some point it has grown though it contained blood. In fact, it contains hemoglo-faster than the average normal …