Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry.

Details

Serval ID
serval:BIB_F7F216857FF0
Type
Article: article from journal or magazin.
Collection
Publications
Title
Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry.
Journal
Blood
Author(s)
Brümmendorf T.H., Holyoake T.L., Rufer N., Barnett M.J., Schulzer M., Eaves C.J., Eaves A.C., Lansdorp P.M.
ISSN
0006-4971
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
95
Number
6
Pages
1883-1890
Language
english
Abstract
Chronic myeloid leukemia (CML) is a clonal, multilineage myeloproliferative disorder characterized by the Philadelphia chromosome (Ph) and a marked expansion of myeloid cells. Previous studies have indicated that the telomere length in blood cells may indicate their replicative history. However, the large variation in telomere length between individuals complicates the use of this parameter in CML and other hematologic disorders. To circumvent this problem, we compared the telomere length in peripheral blood or bone marrow cells with purified normal (Ph(-)) T lymphocytes from the same CML patient using fluorescence in situ hybridization and flow cytometry. Overall telomere fluorescence was significantly reduced in Ph(+) cells from patients with CML compared to blood leukocytes from normal individuals (P < 0.001) or normal (Ph(-)) T lymphocytes from the same individuals (n = 51, P < 0.001). Cells from patients in accelerated phase or blast phase (AP/BP) showed significantly shorter average telomere length than cells from patients in chronic phase (CP, P = 0.02) or cytogenetic remission (CR, P = 0.03). Patients in CP who subsequently developed BP within 2 years had significantly shorter telomeres than those who did not develop BP for at least 2 years (P < 0.05). Accelerated replication-dependent telomere shortening in Ph(+ )versus Ph(-) leukocytes supports previous evidence that Ph(+) stem cells cycle more actively than their counterparts in normal individuals. Our data further suggest that telomere shortening may serve as a surrogate marker of disease progression in patients with CP CML, supporting a mechanistic link between CML stem cell turnover, genetic instability, and malignant evolution in this disease. (Blood. 2000;95:1883-1890) (Blood. 2000;95:1883-1890)
Keywords
Adolescent, Adult, Age Factors, Aged, Antigens, CD3/isolation & purification, Blast Crisis/genetics, Bone Marrow/ultrastructure, Flow Cytometry, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics, Middle Aged, Philadelphia Chromosome, Prognosis, T-Lymphocytes/ultrastructure, Telomere/physiology, Telomere/ultrastructure, Time Factors, Tumor Cells, Cultured
Pubmed
Web of science
Create date
13/10/2009 8:16
Last modification date
20/08/2019 16:24
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