Impact of telomere length on survival in classic and variant hairy cell leukemia

Leuk Res. 2015 Dec;39(12):1360-6. doi: 10.1016/j.leukres.2015.09.015. Epub 2015 Sep 24.

Abstract

Telomeres, which protect the ends of chromosomes, are shortened in several hematologic malignancies, often with adverse prognostic implications, but their effect on prognosis of classic and variant hairy cell leukemia (HCL and HCLv) has not been reported. HCL/HCLv genomic DNA from 46 patients was studied by PCR to determine the ratio of telomere to single copy gene number (T/S). T/S was unrelated to diagnosis of HCL or HCLv (p=0.27), but shorter T/S was associated with unmutated immunoglobulin rearrangements (p=0.033) and age above the median at diagnosis (p=0.017). Low T/S was associated with shorter overall survival from diagnosis (OS), particularly T/S <0.655 (p=0.0064, adjusted p=0.019). Shorter OS was also associated with presence of unmutated (p<0.0001) or IGHV4-34+ (p<0.0001) rearrangements, or increasing age (p=0.0002). Multivariable analysis with Cox modeling showed that short T/S along with either unmutated or IGHV4-34+ rearrangements remained associated with reduced OS (p=0.0071, p=0.0024, respectively) after age adjustment. While T/S is relatively long in HCL and the disease usually indolent with excellent survival, shortened telomeres in HCL/HCLv are associated with decreased survival. Shortened T/S could represent a risk factor needing further investigation/intervention to determine if non-chemotherapy treatment options, in addition to or instead of chemotherapy, might be particularly useful.

Keywords: Chromosomes; DNA damage; Hairy cell leukemia; Molecular marker; Telomere.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antimetabolites, Antineoplastic / therapeutic use
  • Combined Modality Therapy
  • DNA, Neoplasm / genetics
  • Drug Resistance, Neoplasm
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Leukemia, Hairy Cell / classification
  • Leukemia, Hairy Cell / drug therapy
  • Leukemia, Hairy Cell / genetics*
  • Leukemia, Hairy Cell / mortality
  • Leukemia, Hairy Cell / surgery
  • Leukocyte Count
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Splenectomy
  • Telomere / ultrastructure*
  • Telomere Homeostasis
  • Telomere Shortening*

Substances

  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Immunoglobulin Heavy Chains