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Blood, 15 February 2001, Vol. 97, No. 4, pp. 895-900
HEMATOPOIESIS
Telomere length in leukocyte subpopulations of patients with
aplastic anemia
Tim H. Brümmendorf,
Jaroslaw P. Maciejewski,
Jennifer Mak,
Neal S. Young, and
Peter M. Lansdorp
From the Terry Fox Laboratory, British Columbia Cancer
Agency, and the Department of Medicine, University of British Columbia,
Vancouver, BC, Canada; the Abteilung Hämatologie, Onkologie und
Immunologie, Medizinische Universitätsklinik,
Tübingen, Germany; and the Hematology Branch, National Heart,
Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
In most human cells, the average length of telomere repeats
at the ends of chromosomes provides indirect information about their
mitotic history. To study the turnover of stem cells in patients with
bone marrow failure syndromes, the telomere length in peripheral blood
granulocytes and lymphocytes from patients with aplastic anemia (AA,
n = 56) and hemolytic paroxysmal nocturnal hemoglobinuria (n = 6)
was analyzed relative to age-matched controls by means of fluorescence
in situ hybridization and flow cytometry. The telomere lengths
in granulocytes from patients with AA were found to be significantly
shorter than those in age-adjusted controls (P = .001).
However, surprisingly, telomere length in granulocytes from AA patients
who had recovered after immunosuppressive therapy did not differ
significantly from controls, whereas untreated patients and
nonresponders with persistent severe pancytopenia showed marked and
significant telomere shortening. These results support extensive
proliferation of hematopoietic stem cells in subgroups of AA patients.
Because normal individuals show significant variation in telomere
length, individual measurements in blood cells from AA patients may be
of limited value. Whether sequential telomere length measurements can
be used as a prognostic tool in this group of disorders remains to be clarified.
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