Telomere length in paroxysmal nocturnal hemoglobinuria correlates with clone size
Received 27 March 2007; received in revised form 5 June 2007; accepted 6 June 2007. published online 15 August 2007.
Objective
To study if telomere length can be used as a surrogate marker for the mitotic history in normal and affected hematopoietic cells from patients with paroxysmal nocturnal hemoglobinuria (PNH).
Methods
The telomere length was measured by automated multicolor flow fluorescence in situ hybridization in glycosyl-phosphatidyl-inositol anchored protein (GPI)–negative and GPI-positive peripheral blood leukocytes. Eleven patients were studied, two with predominantly hemolytic PNH and nine with PNH associated with marrow failure.
Results
Telomere length in GPI-negative cells was significantly shorter than in GPI-positive cells of the same patient (p < 0.01, n = 11). The difference in telomere length (telomere length in GPI-positive minus telomere length in GPI-negative cells) correlated with the percentage of GPI-negative white blood cells.
Conclusion
Our results support the hypothesis that telomere length is correlated to the replicative history of GPI-positive and GPI-negative cells and warrant further studies of telomere length in relation to disease progression in PNH.
aTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
bHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
cDepartment of Hematology, University of Bern, Bern, Switzerland
dDepartment of Medicine, University of British Columbia, Vancouver, BC, Canada
Offprint requests to: Peter M. Lansdorp, M.D., Ph.D., Terry Fox Laboratory, 675 West 10th Avenue, 11th Floor, Vancouver, BC, V5Z 1L3, Canada
ABSTRACT