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199406, —анкт-ѕетербург, ул.√аванска€, д. 49, корп.2

ISSN 1999-6314

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Vol. 13, Art. 4 (pp. 38-57)    |    2012       

The modern conception of the proper role of telomeres and telomerase in pathogenesis of hematologic and oncology diseases
The Federal State Entity УRussian Institute for Hematology and TransfusiologyФ of the Federal Medical-Biological Agency (FMBA) of the Russian Federation (191024, St-Petersburg, 2 Sovietskaya Str. 16, phone: 812 7175938, bloodscience@mail.ru)

Brief summary

The modern methods of biomedical research let us get to know a cutting - edge information in the pathology of diseases. Measurement of telomerase activity and telomere length are new highly informative diagnostic tests. There is set of the diseases such as dyskeratosis congenital, aplastic anemia, myelodisplastic syndrome, acute myeloid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma and some other disorders which characterized of genetic instability and telomere alterations. The telomere length changes are representative of processes cell development and degradation. The research of telomere genetic defects and telomere renewal mechanisms are very important for prognosis of disease and treatment choice. The telomere length measurement in peripheral blood leucocytes could be used as a screening method for disease monitoring and prognosis as well as control of treatment efficacy. The telomere length shortening is a strong sign of oncology disease development. The review considers molecular mechanisms of telomere renewal and telomerase activity which could result in hematology disease.

Key words

stem cell, telomere length, telomerase, dyskeratosis congenital, pulmonary fibrosis, aplastic anemia, multiple myeloma, chronic lymphoid leukemia, chronic myeloid leukemia.

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Reference list

1. Blackburn Elizabeth H. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. // FEBS Letters. Ц 2005. Ц Vol.579. Ц P. 859Ц862

2. Cech Thomas R. Beginning to Understand the End Review of the Chromosome. // Cell. Ц 2004. Ц Vol. 116, P. 273Ц279

3. Calado Rodrigo T. and Young Neal S. Telomere maintenance and human bone marrow failure. // BLOOD. Ц 2008. Ц Vol.111. Ц є 9. Ц P. 4446-4455

4. Calado Rodrigo T., Young Neal S. Telomere Diseases. // N Engl J Med. Ц 2009. Ц Vol. 361. Ц P.2353-2365

5. Gammaitoni Loretta, Weisel Katja C., Gunetti Monica, Kai-Da Wu, Bruno Stefania, Pinelli Silvana, Bonati Antonio, Aglietta Massimo, Moore Malcolm A. S., Piacibello Wanda. Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. // BLOOD. Ц 2004. Ц Vol. 103. Ц є 12. Ц P. 4440-4448

6. Kirwan Michael, Dokal Inderjeet. Dyskeratosis congenita, stem cells and telomeres. // Biochim Biophys Acta. Ц 2009. Ц Vol.1792(4). Ц P.371Ц379

7. Brümmendorf Tim H., Maciejewski Jaroslaw P., Mak Jennifer, Young Neal S. and Lansdorp Peter M. Telomere length in leukocyte subpopulations of patients with aplastic Anemia. // BLOOD. Ц 2001. Ц Vol 97. Ц є 4. Ц P.895-900

8. Grabowski Pawel, Hultdin Magnus, Karlsson Karin, Tobin Gerard, Åleskog Anna, Thunberg Ulf, Laurell Anna, Sundstrom Christer, Rosenquist Richard, Roos Goran. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. // BLOOD. Ц 2005 Ц Vol 105. Ц є 12. Ц P. 4807-12.

9. Roos Göran, Kröber Alexander, Grabowski Pawel, Kienle Dirk, Bühler Andreas, Döhner Hartmut, Rosenquist Richard, Stilgenbauer Stephan. Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. // BLOOD. Ц 2008. Ц V 111. Ц є 4. Ц P.2246-2252

10. Campbell LJ, Fidler C, Eagleton H, Peniket A, Kusec R, Gal1 S, Littlewood TJ, Wainscoat JS and Boultwood J. hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia. // Leukemia. Ц 2006. Ц є 20. Ц P.671Ц679

11.Drummond Mark W., Lennard Anne, Brûmmendorf Tim H., Holyoake Tessa L. Telomere Shortening Correlates with Prognostic Score at Diagnosis and Proceeds Rapidly during Progression of Chronic Myeloid Leukemia. // Leukemia & Lymphoma. Ц 2004. Ц Vol. 45 (9). Ц P.1775Ц1781

12.Yamaguchi H, Calado RT, Ly H, et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. // N Engl J Med. Ц 2005. Ц Vol.352. Ц P.1413-24

13. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. // Genes Dev. Ц 2005. Ц Vol.19. P.2100-10

14. Blasco MA. Telomere length, stem cells and aging. // Nat Chem Biol. Ц 2007. Ц Vol.3. Ц P.640-9

15. Sarin KY, Cheung P, Gilisonee E, et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. // Nature. Ц 2005. Ц Vol.436. Ц P.1048-52

16. Choi J, Southworth LK, Sarin KY, et al. TERT promotes epithelial proliferation through transcriptional control of a Mycand Wnt-related developmental program. // PLoS Genet. Ц 2008. Ц Vol.4(1) Ц 10

17.Walne AJ, Vulliamy T, Marrone A, et al. Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomeraseassociated protein NOP10. // Hum Mol Genet. Ц 2007. Ц Vol.16. Ц P.1619-29.

18.Vulliamy T, Beswick R, Kirwan M, et al. Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. // Proc Natl Acad Sci USA 2008. Ц Vol.105. Ц P.8073-8

19. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. // Am J Hum Genet. Ц 2008. Ц Vol.82. P.501-9

20.Alter BP, Baerlocher GM, Savage SA, et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. // Blood. Ц 2007. Ц Vol.110. Ц P.1439-47

21.Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. // Nat Genet. Ц 2004. Ц Vol.36. Ц P.447-9

22.Marrone A, Stevens D, Vulliamy T, Dokal I, Mason PJ. Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency. // Blood. Ц 2004. Ц Vol. 104. Ц P.3936-40

23. Calado RT, Yewdell WT, Wilkerson KL, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. // Blood. Ц 2009. Ц Vol.114. Ц P.2236-43

24. Savage SA, Dokal I, Armanios M, et al. Dyskeratosis congenita: the first NIH clinical research workshop. // Pediatr Blood Cancer. Ц 2009. Ц Vol.53. Ц P.520-3

25. Calado RT, Young NS. Telomere maintenance and human bone marrow failure. // Blood. Ц 2008. Ц Vol.111. Ц P.4446-55

26.Armanios M, Chen J-L, Chang Y-PC, et al. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. // Proc Natl Acad Sci USA. Ц 2005. Ц Vol.102. Ц P.15960-4

27.Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. // N Engl J Med. Ц 2007. Ц Vol.356. Ц P.1317-26

28. Tsakiri KD, Cronkhite JT, Kuan PJ, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. // Proc Natl Acad Sci USA. Ц 2007. Ц Vol.104. Ц P.7552-7

29.Mushiroda T, Wattanapokayakit S, Takahashi A, et al. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. // J Med Genet. Ц 2008. Ц Vol.45. Ц P.654-6

30.Alder JK, Chen JJ, Lancaster L, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. // Proc Natl Acad Sci USA. Ц 2008. Ц Vol.105. Ц P.13051-6

31. Calado RT, Regal JA, Kleiner DE, et al. A spectrum of severe liver and blood disorders associated with telomerase mutations. // PLoS One. Ц 2009. Ц Vol.4(11). Ц P. 7926

32. Talbot-Smith A, Syn WK, MacQuillan G, Neil D, Elias E, Ryan P. Familial idiopathic pulmonary fibrosis in association with bone marrow hypoplasia and hepatic nodular regenerative hyperplasia: a new УtrimorphicФ syndrome. // Thorax. Ц 2009. Ц Vol.64. Ц P.440-3

33.Gonzalez-Huezo MS, Villela LM, Zepeda-Florencio MC, Carrillo-Ponce CS, Mondragon-Sanchez RJ. Nodular regenerative hyperplasia associated to aplastic anemia: a case report and literature review. // Ann Hepatol. Ц 2006. Ц Vol.5. Ц P.166-9

34. Boveri T. Concerning the origin of malignant tumours. / Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press and The Company of Biologists, 2008.

35. Finkel T, Serrano M, Blasco MA. The common biology of cancer and ageing. // Nature. Ц 2007. Ц Vol.448. Ц P.767-74

36. de Lange T. Telomere-related genome instability in cancer. // Cold Spring Harb Symp Quant Biol. Ц 2005. Ц Vol.70. Ц P.197-204

37. Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. // Nat Med. Ц 2006. Ц Vol.12. Ц P.1133-8

38. Risques RA, Vaughan TL, Li X, et al. Leukocyte telomere length predicts cancer risk in BarrettТs esophagus. // Cancer Epidemiol Biomarkers Prev. Ц 2007. Ц Vol.16. Ц P.2649-55

39. Finley JC, Reid BJ, Odze RD, et al. Chromosomal instability in BarrettТsesophagus is related to telomere shortening. // Cancer Epidemiol Biomarkers Prev. Ц 2006. Ц Vol.15. Ц P.1451-7

40. Liu X, Bao G, Huo T, Wang Z, He X, Dong G. Constitutive telomere length and gastric cancer risk: case-control analysis in Chinese Han population. // Cancer Sci. Ц 2009. Ц Vol.100. Ц P.1300-5

41. Jang JS, Choi YY, Lee WK, et al. Telomere length and the risk of lung cancer. // Cancer Sci. Ц 2008. Ц Vol.99. Ц P.1385-9

42.Mirabello L, Huang W-Y, Wong JY, et al. The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer. // Aging Cell. Ц 2009. Ц Vol.8. Ц P.405-13

43.Gebre-Medhin S, Broberg K, Jonson T, et al. Telomeric associations correlate with telomere length reduction and clonal chromosome aberrations in giant cell tumor of bone. // Cytogenet Genome Res. Ц 2009. Ц Vol. 124. Ц P.121-7

44.Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. // Blood. Ц 2009. Ц Vol.113. Ц P.6549-57

45. Cooper JN, Calado R, Wu C, Scheinberg P, Young N. Telomere length of peripheral blood leukocytes predicts relapse and clonal evolution after immunosuppressive therapy in severe aplastic anemia. // Presented at the 50th annual meeting of the American Society of Hematology, San Francisco, December 6Ц9. Ц 2008. Ц P. 108

46. Calado RT, Regal JA, Hills M, et al. Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. // Proc Natl Acad Sci USA. Ц 2009. Ц Vol.106. Ц P.1187-92

47. Chakraborty S, Sun C-L, 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. Ц 2009. Ц Vol.27. Ц P.791-8

48. Swiggers SJJ, Kuijpers MA, de Cort MJM, Beverloo HB, Zijlmans MJM. Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes. // Genes Chromosomes Cancer. Ц 2006. Ц Vol.45. Ц P.247-56

49. Sieglova Z, Zilovcova S, Cermak J, et al. Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis? // Leuk Res. Ц 2004. Ц Vol.28. Ц P.1013-21

50. Rafnar T, Sulem P, Stacey SN, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. // Nat Genet. Ц 2009. Ц Vol.41. Ц P.221-7

51.McKay JD, Hung RJ, Gaborieau V, et al. Lung cancer susceptibility locus at 5p15.33. // Nat Genet. Ц 2008. Ц Vol.40. Ц P.1404-6

52.Hosgood HD III, Cawthon RM, He X, Chanock SJ, Lan Q. Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility. // Lung Cancer 2009. Ц Vol.44. Ц P.1832-38

53. Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. // Nat Genet. Ц 2009. Ц Vol.41. Ц P.899-904

54. Chen M, Ye Y, Yang H, et al. Genomewide profiling of chromosomal alterations in renal cell carcinoma using highdensity single nucleotide polymorphism arrays. // Int J Cancer. - 2009. Ц Vol.125. Ц P.2342-8

55. Stacey SN, Sulem P, Masson G, et al. New common variants affecting susceptibility to basal cell carcinoma. // Nat Genet. Ц 2009. Ц Vol.41. Ц P.909-14

56. Savage SA, Chanock SJ, Lissowska J, et al. Genetic variation in five genes important in telomere biology and risk for breast cancer. // Br J Cancer. Ц 2007. Ц Vol.97. Ц P.832-6

57. Folini M, Gandellini P, Zaffaroni N. Targeting the telosome: therapeutic implications. // Biochim Biophys Acta. Ц 2009. Ц Vol.1792. Ц P.309-16

58.Armstrong L, Saretzki G, Peters H, et al. Overexpression of telomerase confers growth advantage, stress resistance, and enhanced differentiation of ESCs toward the hematopoietic lineage. // Stem Cells. Ц 2005. Ц Vol.23. Ц P.516-29

59.Huda N, Tanaka H, Herbert BS, Reed T, Gilley D. Shared environmental factors associated with telomere length maintenance in elderly male twins. // Aging Cell. Ц 2007. Ц Vol.6. Ц P.709-13

60. von Zglinicki T, Saretzki G, Ladhoff J, dТAdda di Fagagna F, Jackson SP. Human cell senescence as a DNA damage response. // Mech Ageing Dev. Ц 2005. Ц Vol.126. Ц P.111-7

61. Satoh M, Minami Y, Takahashi Y, Tabuchi T, Itoh T, Nakamura M. Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease. // Clin Sci (Lond). Ц 2009. Ц Vol.116. Ц P.827-35

62. Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. // Lancet. Ц 2007. Ц Vol.369. Ц P.107-14

63. Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the Cardiovascular Health Study. // Am J Epidemiol. Ц 2007. Ц Vol.165. Ц P.14-21

64. Farzaneh-Far R, Cawthon RM, Na B, Browner WS, Schiller NB, Whooley MA. Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study. // Arterioscler Thromb Vasc Biol. Ц 2008. Ц Vol.28. Ц P.1379-84

65.OТDonnell CJ, Demissie S, Kimura M, et al. Leukocyte telomere length and carotid artery intimal medial thickness: the Framingham Heart Study. // Arterioscler Thromb Vasc Biol. Ц 2008. Ц Vol.28. Ц P.1165-71

66. Stewart SA, Weinberg RA. Telomeres: cancer to human aging. // Annu Rev Cell Dev Biol. Ц 2006. Ц Vol.22. Ц P.531-57

67. Jiang H, Schiffer E, Song Z, et al. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. // Proc Natl Acad Sci USA. Ц 2008. Ц Vol.105. Ц P.11299-304

68. Bayne S, Liu J-P. Hormones and growth factors regulate telomerase activity in ageing and cancer. // Mol Cell Endocrinol. Ц 2005. Ц Vol.240. Ц P.11-22

69. Beyne-Rauzy O, Prade-Houdellier N, Demur C, et al. Tumor necrosis factoralpha inhibits hTERT gene expression in human myeloid normal and leukemic cells. // Blood. Ц 2005. Ц Vol.106. Ц P.3200-5

70.Woo J, Suen EW, Leung JC, Tang NL, Ebrahim S. Older men with higher selfrated socioeconomic status have shorter telomeres. // Age Ageing. Ц 2009. Ц Vol.38. Ц P.553-8

71.Marco Ladetto. Telomere disrupts, CLL progresses. // Blood. Ц 2010. Ц Vol.16. Ц є 11. Ц P.1821 Ц 1822

72. Lin TT, Letsolo BT, Jones RE, et al. Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis. // Blood. Ц 2010. Ц Vol.116. Ц є 11. Ц P.1899-1907

73.Kai-Da Wu, Lisa M. Orme, John Shaughnessy, Jr, Joth Jacobson, Bart Barlogie, and Malcolm A. S. Moore. Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, andoverall survival. // Blood. Ц 2003. Ц Vol.101. Ц P.4982-4989

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