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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 358-361
BRIEF REPORT
Telomere length shortening in chronic myelogenous leukemia is
associated with reduced time to accelerated phase
Jackie Boultwood,
Andrew Peniket,
Fiona Watkins,
Patricia Shepherd,
Paul McGale,
Susan Richards,
Carrie Fidler,
Timothy J. Littlewood, and
James S. Wainscoat
From the Leukaemia Research Fund Molecular Haematology Unit,
Department of Cellular Science, John Radcliffe Hospital, Oxford;
MRC CML Trials Unit, Western General Hospital, Edinburgh; CTSU,
Radcliffe Infirmary, Oxford, UK.
Telomere shortening is associated with disease evolution in chronic
myelogenous leukemia (CML). We have examined the relationship between
diagnostic telomere length and outcome in 59 patients with CML who
entered into the MRC CMLIII Trial by Southern blot hybridization using
the (TTAGGG)4 probe. Age-adjusted telomere repeat array
(TRA) reduction was found to significantly correlate with time from
diagnosis to acceleration, such that patients with a larger TRA
reduction entered the accelerated phase more rapidly (r =  0.50; P = .008). Cox-regression
analysis for this group was suggestive of a relationship between a
greater TRA-reduction and a shorter time to acceleration
(P = .054). Age-adjusted TRA reduction did not
significantly affect either the time to blast crisis or overall
survival. Our results show that telomere shortening observed at the
time of diagnosis in CML significantly influences the time to progress
to the accelerated phase. The measurement of diagnostic TRA may prove
to be clinically important in the selection of patients at high risk of
disease transformation in CML.
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