Telomere Length Identifies Two Distinct Populations with Different Outcome among VH-Unmutated CLL Patients

Introduction Telomere restriction fragments (TRF) length is a well-known prognostic indicator in CLL. Long telomeres have been associated with VH-mutated status, while VH-unmutated patients are regarded as having uniformly short telomeres. However, little is known on cases in which discordance exists between these two parameters. Patients and methods 138 B-CLL patients were analyzed for TRF length and VH mutational status. All samples were taken before the start of anti-CLL treatment. M/F ratio was 93/45. Median age was 60 years. According to Binet staging, 82 patients were A, 30 B and 26 C. CD38 and ZAP70 expression and FISH for Ch 11, 12, 13, 17, were available in 72% of patients. Median follow-up was 33 months (range 6–290). TRF length was evaluated by Southern blot as previously described (Ladetto M et al, Blood 2004). VH mutational status was evaluated by direct sequencing according to standard methods. Results VH sequencing was successful in 127 patients: 82 were VH-mutated and 45 VH-unmutated. Median TRF length was 6097bp (1465–14837). As expected VH-unmutated patients had shorter telomeres (median 4000bp) compared to VH-mutated patients (median 7399bp) (p 99% vs H 98%). In addition they showed no difference for all the available (previously mentioned) biological and clinical parameters. However the two population had significant differences in terms of clinical outcome: 5-year PFS was 22% in concordant patients and 55% in discordant (p