Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): No evidence for intrinsic growth advantage of PNH clones Journal Article

  


Authors: Araten, D. J.; Bessler, M.; McKenzie, S.; Castro-Malaspina, H.; Childs, B. H.; Boulad, F.; Karadimitris, A.; Notaro, R.; Luzzatto, L.
Article Title: Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): No evidence for intrinsic growth advantage of PNH clones
Abstract: 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.
Keywords: pathogenesis; flow cytometry; erythrocytes; paroxysmal nocturnal hemoglobinuria; aplastic anemia; cells; abnormalities; somatic mutations; cyclosporine-a; eradication; myelodysplasia; granulocytes; aplastic-anemia; clonal diseases; normal individuals
Journal Title: Leukemia
Volume: 16
Issue: 11
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2002-11-01
Start Page: 2243
End Page: 2248
Language: English
ACCESSION: WOS:000179193400010
DOI: 10.1038/sj.leu.2402694
PROVIDER: wos
PUBMED: 12399968
Notes: Article -- Source: Wos
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MSK Authors
  1. Farid Boulad
    329 Boulad
  2. Barrett H Childs
    74 Childs
  3. Anastasios Karadimitris
    13 Karadimitris
  4. Hugo Castro-Malaspina
    333 Castro-Malaspina
  5. David Araten
    20 Araten
  6. Lucio Luzzatto
    105 Luzzatto
  7. Susan Mckenzie
    16 Mckenzie
  8. Monica M. Bessler
    33 Bessler
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