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Blood, 15 July 2005, Vol. 106, No. 2, pp. 531-533.
Prepublished online as a Blood First Edition Paper on April 5, 2005; DOI 10.1182/blood-2004-10-3996.
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Submitted October 15, 2004
Accepted March 6, 2005
Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)-negative as compared to GPI-positive granulocytes from patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) detected by Proaerolysin Flow-Fish
Fabian Beier, Stefan Balabanov, Tom Buckley, Klaus Dietz, Ulrike Hartmann, Markus Rojewski, Lothar Kanz, Hubert Schrezenmeier, and Tim H Brummendorf*
Division of Hematology, Oncology and Immunology, University of Tuebingen, Tuebingen, Germany
Department of Biochemistry and Microbiology, University of Victoria, Victoria, B.C., Canada
Department of Medical Biometry, University of Tuebingen, Tuebingen, Germany
Department of Transfusion Medicine, University of Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
* Corresponding author; email: t.bruemmendorf{at}uke.uni-hamburg.de.
Telomere length has been linked to disease stage and degree of (pan-)cytopenia in patients with bone marrow failure syndromes. The aim of the current study was to analyze the impact of replicative stress on telomere length in residual GPI(+) vs. GPI(-) hematopoiesis in patients with PNH. Peripheral blood granulocytes from 16 patients and 22 healthy individuals were analyzed. For this purpose, we developed Proaerolysin flow-FISH, a novel methodology which combines Proaerolysin staining (for GPI expression) with flow-FISH (for telomere length measurement). We found significantly shortened telomeres in GPI(-) granulocytes (mean ± SE: 6.26 ± 0.27 telomere fluorescence units (TFU), both compared to their GPI(+) counterparts (6.88 ± 0.38 TFU; p=0.03) as well as to age-matched healthy individuals (7.73 ± 0.23 TFU; p< 0.001). Our findings are in support of a selective growth advantage model of PNH assuming that damage to the GPI(+) HSC compartment leads to compensatory hyperproliferation of residual GPI(-) HSC.

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