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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.
HEMATOPOIESIS Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISHFrom the Division of Hematology, Oncology and Immunology, and the Department of Medical Biometry, University of Tübingen, Germany; the Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC; and the Department of Transfusion Medicine, University of Ulm, and Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany.
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 glycosylphosphatidylinositol-positive (GPI+) versus GPI hematopoiesis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Peripheral blood granulocytes from 16 patients and 22 healthy individuals were analyzed. For this purpose, we developed proaerolysin flow-FISH, a novel methodology that 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 with their GPI+ counterparts (6.88 ± 0.38 TFU; P = .03) as well as with age-matched healthy individuals (7.73 ± 0.23 TFU; P < .001). Our findings are in support of a selective growth advantage model of PNH assuming that damage to the GPI+ hematopoietic stem-cell (HSC) compartment leads to compensatory hyperproliferation of residual GPIHSCs.
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