Telomere length in leukocyte subpopulations of patients with aplastic anemia

Telomere length in leukocyte subpopulations of patients with aplastic anemia
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DOI:
10.1182/blood.v97.4.895
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发表时间:
2001-02-15
期刊:
影响因子:
20.3
通讯作者:
Lansdorp, PM
Lansdorp, PM
中科院分区:
医学1区
文献类型:
--
作者:
Brümmendorf, TH;Maciejewski, JP;Lansdorp, PM

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在大多数人类细胞中,染色体末端端粒重复序列的平均长度提供了有关其有丝分裂历史的间接信息。为了研究骨髓衰竭综合征患者的干细胞更新,采用荧光原位杂交和流式细胞术分析了再生障碍性贫血(AA,n = 56)和溶血性阵发性睡眠性血红蛋白尿症(n = 6)患者外周血粒细胞和淋巴细胞的端粒长度,并与年龄匹配的对照组进行比较。AA患者的粒细胞端粒长度明显短于年龄调整后的对照组(P =.001)。然而,令人惊讶的是,免疫抑制治疗后恢复的AA患者的粒细胞端粒长度与对照组没有显著差异,而未治疗的患者和持续严重全血细胞减少的无应答者显示出明显的端粒缩短。这些结果支持AA患者亚组中造血干细胞的广泛增殖。由于正常人显示端粒长度的显着变化,个体测量AA患者的血细胞可能是有限的价值。是否连续端粒长度测量可以作为一种预后工具,在这组疾病仍有待澄清。(C)2001年,美国血液学会。
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.(C) 2001 by The American Society of Hematology.