Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status.
B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin V(H) genes have better outcome than unmutated cases. V(H)-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, V(H) gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the V(H)-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining V(H) mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.
Grabowski
Pawel
P
Department of Medical Biosciences, Pathology, Umeå University, SE-90187 Umeå, Sweden.
Hultdin
Magnus
M
Karlsson
Karin
K
Tobin
Gerard
G
Aleskog
Anna
A
Thunberg
Ulf
U
Laurell
Anna
A
Sundström
Christer
C
Rosenquist
Richard
R
Roos
Göran
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors; D016896:Treatment Outcome
D007143:Immunoglobulin Heavy Chains