¹Department of Medicine, Hematology Division, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

²Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

³Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁴IST, Instituto Nazionale per la Ricerca sul Cancro, Genova, Italy

Correspondence to: L Luzzatto, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy; Fax: +39 010 355573; E-mail: lucio.luzzatto@istge.it

PNH is characterized by expansion of one or more stem cell clones with a PIG-A mutation, which causes a severe deficiency in the expression of glycosylphosphatidylinositol (GPI)-anchored proteins. There is evidence that the expansion of PIG-A mutant clones is concomitant with negative selection against PIG-A wild-type stem cells by an aplastic marrow environment. We studied 36 patients longitudinally by serial flow cytometry, and we determined the proportion of PNH red cells and granulocytes over a period of 1-6 years. We observed expansion of the PNH blood cell population(s) (at a rate of over 5% per year) in 12 out of 36 patients; in all other patients the PNH cell population either regressed or remained stable. The dynamics of the PNH cell population could not be predicted by clinical or hematologic parameters at presentation. These data indicate that in most cases the PNH cell expansion has already run its course by the time of diagnosis. In addition, since in most cases no further expansion takes place, we can infer that the tendency to overgrow normal cells is not an intrinsic property of the PNH clone.

Leukemia (2002) 16, 2243-2248. doi:10.1038/sj.leu.2402694

paroxysmal nocturnal hemoglobinuria; clonal diseases; aplastic anemia; myelodysplasia; flow cytometry