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Post-Transplant Events

Comparative assessment of telomere length before and after hematopoietic SCT: role of grafted cells in determining post-transplant telomere status

Bone Marrow Transplantation volume 45, pages 505–512 (2010)Cite this article

Abstract

Our objective was to characterize the role of grafted cells in determining telomere length (TL) after hematopoietic SCT (HSCT). A total of 20 patients undergoing autografts had PBSC collected after two sequential mobilization courses: TL in the first collection was significantly longer than in the second. For their autografts, 10 patients used PBSC from the first collection and 10 from the second. TL was also investigated before and after HSCT and on the graft in 10 allogeneic HSCT. After autografting, patients receiving PBSC from the first collection had BM TL reflecting that of grafted cells (median bp: 7730 on PBSC vs 7610 on post-HSCT BM, P=NS) and significantly longer than TL of the second collection; analogously, patients autografted with PBSC from the second collection had BM TL reflecting that of grafted cells (7360 on PBSC vs 7120 on post-HSCT BM, P=NS) and significantly shorter compared with the first collection. In the allograft setting, eight patients had their pre-transplant TL significantly shorter than donor PBSC (5960 vs 7110; P=0.0005); following HSCT, BM TL (median 7380 bp) was identical to that of the graft (P=NS). We conclude that grafted cells have a major role in determining TL after HSCT.

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References

  1. Blackburn EH . Structure and function of telomeres. Nature 1991; 350: 569–573.

    Article  CAS  PubMed  Google Scholar 

  2. Zakian VA . Telomeres: beginning to understand the end. Science 1995; 270: 1601–1607.

    Article  CAS  PubMed  Google Scholar 

  3. Van Steensel B, Smogorzewska A, deLange T . TRF2 protects human telomeres from end-to-end fusions. Cell 1998; 92: 401–413.

    Article  CAS  PubMed  Google Scholar 

  4. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H et al. Mammalian telomeres end in a large duplex loop. Cell 1999; 97: 503–514.

    Article  CAS  PubMed  Google Scholar 

  5. Lansdorp PM . Telomeres, stem cells and hematology. Blood 2008; 111: 1759–1766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM et al. Structure and variability of human chromosome ends. Mol Cell Biol 1990; 10: 518–527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Martens UM, Chavez EA, Poon SS, Schmoor C, Lansdorp PM . Accumulation of short telomeres in human fibroblasts prior to replicative senescence. Exp Cell Res 2000; 256: 291–299.

    Article  CAS  PubMed  Google Scholar 

  8. Greider CW . Telomeres, telomerase and senescence. Bioassays 1990; 12: 363–369.

    Article  CAS  Google Scholar 

  9. Harley CB . Telomere loss: mitotic clock or genetic time bomb? Mutat Res 1991; 256: 271–282.

    Article  CAS  PubMed  Google Scholar 

  10. Lindsey J, McGill NI, Lindsey LA, Green DK, Cooke HJ . In vivo loss of telomeric repeats with age in humans. Mutat Res 1991; 256: 45–48.

    Article  CAS  PubMed  Google Scholar 

  11. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992; 89: 10114–10118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC . Telomere reduction in human colorectal carcinoma and with aging. Nature 1990; 346: 866–868.

    Article  CAS  PubMed  Google Scholar 

  13. Vaziri H, Schächter F, Uchida I, Wei L, Zhu X, Effros R et al. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet 1993; 52: 661–667.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Furugori E, Hirayama R, Nakamura KI, Kammori M, Esaki Y, Takubo K . Telomere shortening in gastric carcinoma with aging despite telomerase activation. J Cancer Res Clin Oncol 2000; 126: 481–485.

    Article  CAS  PubMed  Google Scholar 

  15. 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: 492–495.

    Article  PubMed  Google Scholar 

  16. Akiyama M, Asai O, Kuraishi Y, Urashima M, Hoshi Y, Sakamaki H et al. Shortening of telomere in recipients of both autologous and allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2000; 25: 441–447.

    Article  CAS  PubMed  Google Scholar 

  17. Wynn RF, Cross MA, Hatton C, Will AM, Lashford LS, Dexter TM et al. Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet 1998; 351: 178–181.

    Article  CAS  PubMed  Google Scholar 

  18. Seligman SJ . Telomere shortening in recipients of bone-marrow transplants. Lancet 1998; 351: 1287–1288.

    Article  CAS  PubMed  Google Scholar 

  19. Mathioudakis G, Storb R, McSweeney PA, Torok-Storb B, Lansdorp PM, Brümmendorf TH et al. Polyclonal hematopoiesis with telomere shortening in human long term allogeneic marrow graft recipients. Blood 2000; 96: 3991–3994.

    CAS  PubMed  Google Scholar 

  20. Rufer N, Brümmendorf TH, Chapuis B, Helg C, Lansdorp PM, Roosnek E . Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 2001; 97: 575–577.

    Article  CAS  PubMed  Google Scholar 

  21. Roelofs H, de Pauw ES, Zwinderman AH, Opdam SM, Willemze R, Tanke HJ et al. Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation. Blood 2003; 101: 358–362.

    Article  CAS  PubMed  Google Scholar 

  22. Bhatia R, Van Heijzen K, Palmer A, Komiya A, Slovak ML, Chang KL et al. Longitudinal assessment of hematopoietic abnormalities after autologous hematopoietic cell transplantation for lymphoma. J Clin Oncol 2005; 23: 6699–6711.

    Article  PubMed  Google Scholar 

  23. Schröder CP, Wisman GB, de Jong S, van der Graaf WT, Ruiters MH, Mulder NH et al. Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation. Br J Cancer 2001; 84: 1348–1353.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ricca I, Compagno M, Ladetto M, Rocci A, Dell'Aquila M, Omedè P 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: 644–651.

    Article  CAS  PubMed  Google Scholar 

  25. Widmann T, Kneer H, Konig J, Hermann M, Pfreundschuh M . Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation. Exp Haemtol 2008; 36: 104–110.

    Article  CAS  Google Scholar 

  26. Tarella C, Zallio F, Caracciolo D, Cherasco C, Bondesan P, Gavarotti P et al. Hemopoietic progenitor cell mobilization and harvest following an intensive chemotherapy debulking in indolent lymphoma patients. Stem Cells 1999; 17: 55–61.

    Article  CAS  PubMed  Google Scholar 

  27. Tarella C, Di Nicola M, Caracciolo D, Zallio F, Cuttica A, Omedè P et al. High-dose Ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization. Bone Marrow Transplant 2002; 30: 725–732.

    Article  CAS  PubMed  Google Scholar 

  28. Magni M, Di Nicola M, Devizzi L, Matteucci P, Lombardi F, Gandola L et al. Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000; 96: 854–861.

    Google Scholar 

  29. Tarella C, Zanni M, Magni M, Benedetti F, Patti C, Barbui T et al. Rituximab improves the therapeutic efficacy of high-dose chemotherapy with autograft for high-risk follicular and diffuse large B-cell lymphoma: a multicenter GITIL survey of 745 patients. J Clin Oncol 2008; 26: 3166–3175.

    Article  CAS  PubMed  Google Scholar 

  30. Tarella C, Zallio F, Caracciolo D, Cuttica A, Corradini P, Gavarotti P et al. High-dose mitoxantrone+melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity. Leukemia 2001; 15: 256–263.

    Article  CAS  PubMed  Google Scholar 

  31. Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F et al. Reduced intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002; 99: 75–82.

    Article  CAS  PubMed  Google Scholar 

  32. Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021–2030.

    Article  CAS  PubMed  Google Scholar 

  33. Harley CB . Telomeres and aging. In: Blackburn EH, Greider CW (eds). Telomeres. Cold Spring Harbor Laboratory: New York, 1995, pp 247–265.

    Google Scholar 

  34. Rocci A, Ricca I, Dellacasa C, Longoni P, Compagno M, Francese R et al. Long-term lymphoma survivors following high-dose chemotherapy and autograft: evidence of permanent telomere shortening in myeloid cells associated with marked reduction of bone marrow hematopoietic stem cell reservoir. Exp Hematol 2007; 35: 673–681.

    Article  CAS  PubMed  Google Scholar 

  35. Shay JW . Accelerated telomere shortening in bone marrow recipients. Lancet 1998; 351: 153–154.

    Article  CAS  PubMed  Google Scholar 

  36. Brümmendorf TH, Rufer N, Baerlocher GM, Roosnek E, Lansdorp PM . Limited telomere shortening in hematopoietic stem cells after transplantation. Ann N Y Acad Sci 2001; 938: 1–7.

    Article  PubMed  Google Scholar 

  37. Robertson JD, Testa NG, Russell NH, Jackson G, Parker AN, Milligan DW et al. Accelerated telomere shortening following allogeneic transplantation is independent of the cell source and occurs within the first year post transplant. Bone Marrow Transplant 2001; 27: 1283–1286.

    Article  CAS  PubMed  Google Scholar 

  38. Baerlocher GM, Rovó A, Müller A, Matthey S, Stern M, Halter J et al. Cellular senescence of white blood cells in very long-term survivors after allogeneic hematopoietic stem cell transplantation: the role of chronic graft-versus-host disease and female donor sex. Blood 2009; 114: 219–222.

    Article  CAS  PubMed  Google Scholar 

  39. Lahav M, Uziel O, Kestenbaum M, Fraser A, Shapiro H, Radnay J et al. Nonmyeloablative conditioning does not prevent telomere shortening after allogeneic stem cell transplantation. Transplantation 2005; 80: 969–976.

    Article  PubMed  Google Scholar 

  40. Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.

    Article  CAS  PubMed  Google Scholar 

  41. Wu X, Amos CI, Zhu Y, Zhao H, Grossman BH, Shay JW et al. Telomere dysfunction: a potential cancer predisposition factor. J Natl Cancer Inst 2003; 95: 1211–1218.

    Article  CAS  PubMed  Google Scholar 

  42. Beauchamp-Nicoud A, Feneux D, Bayle C, Bernheim A, Léonard C, Koscielny S et al. Therapy-related myelodysplasia and/or acute myeloid leukaemia after autologous haematopoietic progenitor cell transplantation in a prospective single center cohort of 221 patients. Br J Haematol 2003; 122: 109–117.

    Article  PubMed  Google Scholar 

  43. Ricca I, Rocci A, Ruella M, Zanni M, Caracciolo D, Ladetto M et al. The degree of telomere loss in hematopoietic cells correlates with the risk of secondary myelodysplasia/acute leukemia development following autologous stem cell transplantation. Blood (ASH Annual Meeting Abstracts) 2007; 110: 1672.

    Google Scholar 

  44. M′kacher R, Bennaceur-Griscelli A, Girinsky T, Koscielny S, Delhommeau F, Dossou J et al. Telomere shortening and associated chromosomal instability in peripheral blood lymphocytes of patients with Hodgkin's lymphoma prior to any treatment are predictive of second cancers. Int J Radiat Oncol Biol Phys 2007; 68: 465–471.

    Article  PubMed  Google Scholar 

  45. Chakraborty S, Sun CL, Francisco L, Sabado M, Li L, Chang KL 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: 791–798.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Glass B, Kloess M, Bentz M, Schlimok G, Berdel WE, Feller A et al. German high-grade non-Hodgkin lymphoma study group. dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma. Blood 2006; 107: 3058–3064.

    Article  CAS  PubMed  Google Scholar 

  47. Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG et al. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood 2006; 107: 4623–4627.

    Article  CAS  PubMed  Google Scholar 

  48. Tarella C, Zanni M, Di Nicola M, Patti C, Calvi R, Pescarollo A et al. Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Leukemia 2007; 21: 1802–1811.

    Article  CAS  PubMed  Google Scholar 

  49. Beeharry N, Broccoli D . Telomere dynamics in response to chemotherapy. Curr Mol Med 2005; 5: 187–196.

    Article  CAS  PubMed  Google Scholar 

  50. Unryn BM, Hao D, Glück S, Riabowol KT . Acceleration of telomere loss by chemotherapy is greater in older patients with locally advanced head and neck cancer. Clin Cancer Res 2006; 12: 6345–6350.

    Article  CAS  PubMed  Google Scholar 

  51. Wang Y, Schulte BA, Zhou D . Hematopoietic stem cell senescence and long-term bone marrow injury. Cell Cycle 2006; 5: 35–38.

    Article  CAS  PubMed  Google Scholar 

  52. Maccormick RE . Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty? Med Hypotheses 2006; 67: 212–215.

    Article  CAS  PubMed  Google Scholar 

  53. Kastan MB . Our cells get stressed too! Implications for human disease. Blood Cells Mol Dis 2007; 39: 148–150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brosh Jr RM, Bohr VA . Human premature aging, DNA repair and RecQ helicases. Nucleic Acids Res 2007; 35: 7527–7544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lansdorp PM, Dragowska W, Mayani H . Ontogeny-related changes in proliferative potential of human hematopoietic cells. J Exp Med 1993; 178: 787–791.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by grants from Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), Ricerca Finalizzata Regione Piemonte, Ministero della Salute (Rome, Italy) and Michelangelo Foundation for Advances in Cancer Research and Treatment (Milano, Italy).

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  1. M Ruella and A Rocci: These authors contributed equally to this work.

Authors and Affiliations

  1. Dipartimento di Medicina ed Oncologia Sperimentale, Divisione di Ematologia, Università di Torino, Torino, Italy

    M Ruella, A Rocci, C Labetti Bodoni, M Ladetto, D Caracciolo, M Boccadoro & C Tarella

  2. Division Medicina Generale, Ospedale Cottolengo, Torino, Italy

    I Ricca

  3. Molecular Biotechnology Center—Università di Torino, Torino, Italy

    M Ruella & C Tarella

  4. Hematology—BMT Unit, Istituto Nazionale dei Tumori, Milano, Italy

    C Carniti & P Corradini

  5. Oncologia Medica, Istituto Nazionale dei Tumori, Milano, Italy

    C Carlo-Stella

  6. SCDU Ematologia e Terapie Cellulari, AO Mauriziano – Umberto I, Torino, Italy

    M Ruella & C Tarella

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  1. M Ruella
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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 Transplant 45, 505–512 (2010). https://doi.org/10.1038/bmt.2009.297

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