Telomere length in leukocyte subpopulations of patients with aplastic anemia

In most human cells, the average length of telomere repeats at the ends of chromosomes provides indirect information about their mitotic history. To s tudy the turnover of stem cells in patients with bone marrow failure syndro mes, the telomere length in peripheral blood granulocytes and lymphocytes f rom patients with aplastic anemia (AA, n = 56) and hemolytic paroxysmal noc turnal hemoglobinuria (n = 6) was analyzed relative to age-matched controls by means of fluorescence in situ hybridization and flow cytometry. The tel omere lengths in granulocytes from patients with AA were found to be signif icantly shorter than those in age-adjusted controls (P=.001). However, surp risingly, telomere length in granulocytes from AA patients who had recovere d after immunosuppressive therapy did not differ significantly from control s, whereas untreated patients and nonresponders with persistent severe panc ytopenia showed marked and significant telomere shortening. These results s upport extensive proliferation of hematopoietic stem cells in subgroups of AA patients. Because normal individuals show significant variation in telom ere length, individual measurements in blood cells from AA patients may be of limited value. Whether sequential telomere length measurements can be us ed as a prognostic tool in this group of disorders remains to be clarified. (C) 2001 by The American Society of Hematology.