Telomeres are ribonucleoprotein structures which protect the ends of chromosomes from aberrant recombination events and have been reported to be relatively short in several hematologic malignancies; adverse prognosis has been documented in chronic lymphocytic leukemia and several non-B-cell malignancies. However, their association with prognosis of classic and variant hairy cell leukemia (HCL and HCLv) has not been described. To study telomeres in HCL and HCLv, DNA from leukemic cells of patients was measured by monochrome multiplex quantitative PCR (MMQPCR) to determine relative telomere length (RTL). Of 46 patients in the cohort, 5 of 27 HCL (19%) vs. 12 of 19 HCLv (63%) patients had unmutated (>98% homology to germline sequence) immunoglobulin rearrangements (p = 0.0045). IGHV4-34+ rearrangements were present in 12 of the 17 (70%) unmutated cases, including five HCL and seven HCLv. RTL was shown to be shorter in unmutated HCL (p = 0.03) and in patients who had died of their disease (p = 0.03). RTL negatively correlated with IGHV homology to germline sequence (r = -0.331; p = 0.025), and age (r = -0.315; p = 0.035). Shorter RTL was associated with death from disease in either HCL (p = 0.0063) or HCLv (p = 0.0034), in patients with mutated IGHV rearrangements (p = 0.005), or in all patients combined (p = 0.0008). Median survival from diagnosis was less in time in patients with shorter RTL (p = 0.016) and this significant difference persisted when examining just the 19 patients with HCLv (p = 0.029). Gene expression profiling identified several genes related to telomere maintenance with significantly different expression levels between mutated and unmutated cases. This first of kind study in HCL/HCLv suggests that telomeres play a role in the relative pathology of HCL and HCLv and RTL could be used as a prognostic biomarker in gauging the indolent course of these cancers.
Citation Format: Daniel C. Edelman, Evgeny Arons, Holly Stevenson, Allison Gomez, David Petersen, Hong Zhou, Yonghong Wang, Joshua J. Waterfall, Paul S. Meltzer, Robert Kreitman. Analysis of telomere length in classic and variant hairy cell leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5307. doi:10.1158/1538-7445.AM2015-5307