title: Impact of telomere length on survival in classic and variant hairy cell leukemia.
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.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute (NCI), NIH, United States.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Arons
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute (NCI), NIH, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Cancer Genetics Branch, NCI, NIH, United States.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Edelman
authors.affiliation: Cancer Genetics Branch, NCI, NIH, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, 37/5124b, Bethesda, MD 20892-4255, United States.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Cancer Genetics Branch, NCI, NIH, United States.
authors.forename: David
authors.initials: D
authors.lastname: Petersen
authors.affiliation: Cancer Genetics Branch, NCI, NIH, United States.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Genetics Branch, NCI, NIH, United States.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute (NCI), NIH, United States. Electronic address: kreitmar@mail.nih.gov.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
mesh_terms: D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D007943:Leukemia, Hairy Cell / Q000145:classification / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013156:Splenectomy; D016615:Telomere / Q000648:ultrastructure*; D059505:Telomere Homeostasis; D059506:Telomere Shortening
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains
keywords: Chromosomes; DNA damage; Hairy cell leukemia; Molecular marker; Telomere