Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia.
Telomere length is associated with mutation status of the immunoglobulin heavy chain variable (IGHV) gene and clinical course in B-cell chronic lymphocytic leukemia (B-CLL). In a B-CLL cohort of 152 patients, we analyzed telomere length, genomic aberrations, IGHV mutation status, CD38 and ZAP-70 expression to study the prognostic impact and associations among these factors. An inverse correlation existed between telomere length and IGHV homology (P < .001), CD38 (P < .001), and ZAP-70 expression (P = .01). Patients with telomere lengths below median (ie, "short telomeres") and above median (ie, "long telomeres") had similar incidences of genomic aberrations (74% vs 68%), 13q- (57% vs 49%), and +12q (5% vs 12%). In contrast, 13q- as a single aberration was more frequent in patients with long telomeres (51% vs 21%; P = .006), whereas 11q- (27% vs 9%; P = .014), 17p- (17% vs 0%; P < .001), and 2 or more genomic aberrations (39% vs 8%; P < .001) were more frequent in patients with short telomeres. Compared with patients with long telomeres, treatment-free survival (TFS) and overall survival (OS) was significantly shorter (P < .001 and P = .015, respectively) in the group with short telomeres, and telomere length was an independent prognostic indicator for TFS. These observations have biological and prognostic implications in B-CLL.
Roos
Göran
G
Department of Medical Biosciences, Umeå University, Umeå, Sweden. goran.roos@medbio.umu.se
Kröber
Alexander
A
Grabowski
Pawel
P
Kienle
Dirk
D
Bühler
Andreas
A
Döhner
Hartmut
H
Rosenquist
Richard
R
Stilgenbauer
Stephan
S
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D017741:Survivors; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure*
D015703:Antigens, CD; D007135:Immunoglobulin Variable Region