Abstract:
: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 GPI- HSCs.
journal_name
Bloodjournal_title
Bloodauthors
Beier F,Balabanov S,Buckley T,Dietz K,Hartmann U,Rojewski M,Kanz L,Schrezenmeier H,Brümmendorf THdoi
10.1182/blood-2004-10-3996subject
Has Abstractpub_date
2005-07-15 00:00:00pages
531-3issue
2eissn
0006-4971issn
1528-0020pii
2004-10-3996journal_volume
106pub_type
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