Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients.
aging
chemotherapy
lymphoma
telomere
telomere loss
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
revised:
07
12
2022
received:
24
04
2022
accepted:
15
12
2022
medline:
11
8
2023
pubmed:
20
12
2022
entrez:
19
12
2022
Statut:
ppublish
Résumé
Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-342Subventions
Organisme : Fondazione Cariplo
Organisme : Piaggio
Organisme : Banca del Piemonte
Informations de copyright
© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
Références
Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science. 2015;350(6265):1193-1198. https://doi.org/10.1126/science.aab3389
Blackburn EH, Collins K. Telomerase: an RNP enzyme synthesizes DNA. Cold Spring Harb Perspect Biol. 2011;3(5):a003558. https://doi.org/10.1101/cshperspect.a003558
Collins K, Mitchell J. Telomerase in the human organism. Oncogene. 2002;21(4):564-579. https://doi.org/10.1038/sj.onc.1205083
Barrett EL, Richardson DS. Sex differences in telomeres and lifespan. Aging Cell. 2011;10(6):913-921. https://doi.org/10.1111/j.1474-9726.2011.00741.x
Mayer S, Brüderlein S, Perner S, et al. Sex-specific telomere length profiles and age-dependent erosion dynamics of individual chromosome arms in humans. Cytogenet Genome Res. 2006;112(3-4):194-201. https://doi.org/10.1159/000089870
Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266(5193):2011-2015. https://doi.org/10.1126/science.7605428
Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, et al. Association between telomere length and risk of cancer and non-neoplastic diseases: a mendelian randomization study. JAMA Oncol. 2017;3(5):636-651. https://doi.org/10.1001/jamaoncol.2016.5945
Barthel FP, Wei W, Tang M, et al. Systematic analysis of telomere length and somatic alterations in 31 cancer types. Nat Genet. 2017;49(3):349-357. https://doi.org/10.1038/ng.3781
Kroupa M, Rachakonda SK, Liska V, et al. Relationship of telomere length in colorectal cancer patients with cancer phenotype and patient prognosis. Br J Cancer. 2019;121(4):344-350. https://doi.org/10.1038/s41416-019-0525-3
Ricca I, Compagno M, Ladetto M, et al. Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly-spaced high-dose chemotherapy courses with G-CSF. Leukemia. 2005;19(4):644-651. https://doi.org/10.1038/sj.leu.2403652
Ruella M, Rocci A, Ricca I, et al. Comparative assessment of telomere length before and after hematopoietic SCT: role of grafted cells in determining post-transplant telomere status. Bone Marrow Transpl. 2010;45(3):505-512. https://doi.org/10.1038/bmt.2009.297
Wynn RF, Cross MA, Hatton C, et al. Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet. 1998;351(9097):178-181. https://doi.org/10.1016/S0140-6736(97)08256-1
Derenzini E, Risso A, Ruella M, et al. Influence of donor and recipient gender on telomere maintenance after umbilical cord blood cell transplantation: a study by the gruppo italiano trapianto di midollo osseo. Biol Blood Marrow Transpl. 2019;25(7):1387-1394. https://doi.org/10.1016/j.bbmt.2019.03.026
Lu Y, Leong W, Guerin O, Gilson E, Ye J. Telomeric impact of conventional chemotherapy. Front Med. 2013;7(4):411-417. https://doi.org/10.1007/s11684-013-0293-z
Buttiglieri S, Ruella M, Risso A, et al. The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol. 2011;39(12):1171-1181. https://doi.org/10.1016/j.exphem.2011.08.009
Alhareeri AA, Archer KJ, Fu H, et al. Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study. Breast Cancer Res. 2020;22(1):137. https://doi.org/10.1186/s13058-020-01368-6
Song N, Li Z, Qin N, et al. Shortened leukocyte telomere length associates with an increased prevalence of chronic health conditions among survivors of childhood cancer: a report from the st. Jude lifetime cohort. Clin Cancer Res. 2020;26(10):2362-2371. https://doi.org/10.1158/1078-0432.CCR-19-2503
Chakraborty S, Sun CL, Francisco L, et al. Accelerated telomere shortening precedes development of therapy-related myelodysplasia or acute myelogenous leukemia after autologous transplantation for lymphoma. J Clin Oncol. 2009;27(5):791-798. https://doi.org/10.1200/JCO.2008.17.1033
Tarella C, Passera R, Magni M, et al. Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma. J Clin Oncol. 2011;29(7):814-824. https://doi.org/10.1200/JCO.2010.28.9777
Gallicchio L, Gadalla SM, Murphy JD, Simonds NI. The effect of cancer treatments on telomere length: a systematic review of the literature. J Natl Cancer Inst. 2018;110(10):1048-1058. https://doi.org/10.1093/jnci/djy189
Lee JJ, Nam CE, Cho SH, Park KS, Chung IJ, Kim HJ. Telomere length shortening in non-Hodgkin's lymphoma patients undergoing chemotherapy. Ann Hematol. 2003;82(8):492-495. https://doi.org/10.1007/s00277-003-0691-4
Meschia M, Pansini F, Modena AB, et al. Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Matur. 2000;34(2):119-125. https://doi.org/10.1016/s0378-5122(99)00095-x
Frenck RW, Blackburn EH, Shannon KM. The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci USA. 1998;95(10):5607-5610. https://doi.org/10.1073/pnas.95.10.5607
Brüderlein S, Müller K, Melzner J, Hogel J, Wiegand P, Moller P. Different rates of telomere attrition in peripheral lymphocytes in a pair of dizygotic twins with hematopoietic chimerism. Aging Cell. 2008;7(5):663-666. https://doi.org/10.1111/j.1474-9726.2008.00413.x
Viña J, Borrás C, Gambini J, Sastre J, Pallardó FV. Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds. FEBS Lett. 2005;579(12):2541-2545. https://doi.org/10.1016/j.febslet.2005.03.090
Calado RT, Yewdell WT, Wilkerson KL, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood. 2009;114(11):2236-2243. https://doi.org/10.1182/blood-2008-09-178871
Whittemore K, Vera E, Martínez-Nevado E, Sanpera C, Blasco MA. Telomere shortening rate predicts species life span. Proc Natl Acad Sci USA. 2019;116(30):15122-15127. https://doi.org/10.1073/pnas.1902452116
Morton LM, Dores GM, Schonfeld SJ, et al. Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era. JAMA Oncol. 2019;5(3):318-325. https://doi.org/10.1001/jamaoncol.2018.5625
Lex K, Maia Gil M, Lopes-Bastos B, et al. Telomere shortening produces an inflammatory environment that increases tumor incidence in zebrafish. Proc Natl Acad Sci U S A. 2020;117(26):15066-15074. https://doi.org/10.1073/pnas.1920049117