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Telomere shortening correlates with prognostic score at diagnosis and proceeds rapidly during progression of chronic myeloid leukemia

Lookup NU author(s): Dr Anne Lennard


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Chronic myeloid leukemia (CML) is associated increased stem cell turnover. We have previously shown that short telomeres in chronic phase (CP) predict for early progression to blast phase ( BP). Poor prognostic score patients may therefore exhibit increased telomere loss at diagnosis and/or a greater than normal rate of loss during the disease course. We prospectively studied newly diagnosed CML patients for degree of telomere loss; measured telomere length in CML patients at all stages of disease; and performed follow-up sampling according to cytogenetic response to imatinib mesylate. Using flow-FISH, telomere length in peripheral blood leucocytes (PBL) from 32 consecutive newly diagnosed patients was measured ( with ex-vivo expanded T-cells as an internal BCR-ABL negative control), in addition to 65 samples from all CML stages and 7 paired CP/BP samples. Fifty-five normal individuals served as a control population. Patients who attained either a complete cytogenetic response (CCR, 0% Ph+, n = 10) or no CR (100% Ph+, n = 11) underwent follow-up measurement. All statistical tests were two sided. Telomeres in accelerated phase ( AP) and BP patients were significantly shorter than in CP, and mean telomere shortening was significantly greater in high-risk score than low-risk patients (P<0.05) at diagnosis. The rate of shortening during disease progression was 10 - 20 times the rate observed in normal granulocytes. BP samples had undergone at least 30 - 60 additional divisions from baseline Ph- telomere length. Our findings show that telomere shortening in CML is greatest in high-risk score patients at diagnosis, and occurs rapidly during disease progression.

Publication metadata

Author(s): Drummond MW, Lennard A, Brummendorf TH, Holyoake TL

Publication type: Article

Publication status: Published

Journal: Leukemia & Lyphoma

Year: 2004

Volume: 45

Issue: 9

Pages: 1775-1781

ISSN (print): 1042-8194

ISSN (electronic): 1026-8022


DOI: 10.1080/10428190410001693542


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