title: Telomere length shortening in chronic myelogenous leukemia is associated with reduced time to accelerated phase.
abstract: 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.
authors.affiliation: Leukaemia Research Fund Molecular Haematology Unit, Department of Cellular Science, John Radcliffe Hospital, Oxford, UK. jboultwo@worf.molbiol.ox.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Boultwood
authors.forename: A
authors.initials: A
authors.lastname: Peniket
authors.forename: F
authors.initials: F
authors.lastname: Watkins
authors.forename: P
authors.initials: P
authors.lastname: Shepherd
authors.forename: P
authors.initials: P
authors.lastname: McGale
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.forename: C
authors.initials: C
authors.lastname: Fidler
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
authors.forename: J S
authors.initials: JS
authors.lastname: Wainscoat
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001752:Blast Crisis; D015139:Blotting, Southern; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015345:Oligonucleotide Probes; D010976:Platelet Count; D012044:Regression Analysis; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D015345:Oligonucleotide Probes