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

Leukemia volume 16, pages 2243–2248 (2002)Cite this article

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.

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Acknowledgements

We would like to thank Mary Ang, Nimfa Boma, Ruth Rose, Jane Rueda, Nadia Soukhram, and Diane Tabarini for their technical assistance. This work was supported by the Aplastic Anemia Foundation of America New Researcher Award, the Norman and Rosita Winston and the Charles A Dana Foundations, and the National Institute of Health 5RO1 HL56778-03 Grant and Associazione Italiana per la Ricerca sul Cancro.

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Authors and Affiliations

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

    DJ Araten, S McKenzie, H Castro-Malaspina, BH Childs & L Luzzatto

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

    DJ Araten, M Bessler, A Karadimitris & L Luzzatto

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

    F Boulad

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

    R Notaro & L Luzzatto

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  1. DJ Araten
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Correspondence to L Luzzatto.

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Araten, D., Bessler, M., McKenzie, S. et al. Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia 16, 2243–2248 (2002). https://doi.org/10.1038/sj.leu.2402694

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