Myelodysplastic syndromes, aging, and age: Correlations, common mechanisms, and clinical implications

Leukemia and Lymphoma

Volumn 48, Issue 10, 2007, Pages 1900-1909

  Pfeilstöcker, Michael ^a   Karlic, Heidrun ^a   Nösslinger, Thomas ^a   Sperr, Wolfgang ^b   Stauder, Reinhard ^c   Krieger, Otto ^d   Valent, Peter ^b  

^a HANUSCH HOSPITAL   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

^c INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^d ELISABETHINEN HOSPITAL   (Austria)

Author keywords

Aging; Elderly; MDS; Pathophysiology; Prognosis

Indexed keywords

CALCITONIN; CANCER GROWTH FACTOR; CANCER GROWTH FACTOR BETA 1; CD135 ANTIGEN; CHECKPOINT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLIN DEPENDENT KINASE INHIBITOR 2B; GENOMIC DNA; GRANULOCYTE COLONY STIMULATING FACTOR RECEPTOR; INSULIN; MULTIDRUG RESISTANCE PROTEIN 1; PROTEIN BCL 2; PROTEIN MDM2; PROTEIN P14ARF; PROTEIN P53; RAS PROTEIN; STEM CELL FACTOR; UNCLASSIFIED DRUG;

AGING; ALGORITHM; ANGIOGENESIS; APOPTOSIS; CHROMOSOME ABERRATION; CYTOGENETICS; DIETARY INTAKE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA DAMAGE; DNA POLYMORPHISM; DNA SEQUENCE; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE OVEREXPRESSION; GENE TARGETING; GENETIC CODE; GENOMIC INSTABILITY; HEMATOPOIESIS; HEREDITY; HOMEOSTASIS AND REGULATION; HUMAN; IMMUNE RESPONSE; IMMUNITY; INCIDENCE; MORBIDITY; MORTALITY; MYELODYSPLASTIC SYNDROME; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROGNOSIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TELOMERE;

AGE FACTORS; AGED; AGING; ALGORITHMS; CHROMOSOME ABERRATIONS; CYTOGENETICS; DISEASE PROGRESSION; EPIGENESIS, GENETIC; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; NEOVASCULARIZATION, PATHOLOGIC; TELOMERE; TREATMENT OUTCOME;

EID: 35148847401     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.1080/10428190701534382     Document Type: Review

References (124)

1. Bennett, J. M. and Komrokji, R. S. (2005) The myelodysplastic syndromes: diagnosis, molecular biology and risk assessment. Hematology, 10, pp. 258-269.
2. McKenna, R. W. (2004) Myelodysplasia and myeloproliferative disorders in children. Am J Clin Pathol, 122, pp. 58-69.
3. Pfeilstöcker, M., Reisner, R., Nösslinger, T., Grüner, H., Nowotny, H. and Tüchler, H. (1999) Cross-validation of prognostic scores in myelodysplastic syndromes on 386 patients from a single institution confirms importance of cytogenetics. Br J Haematol, 106, pp. 455-463.
4. Germing, U., Hildebrandt, B., Pfeilstöcker, M., Nösslinger, T., Valent, P. and Fonatsch, C. (2005) Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia, 19, pp. 2223-2231.
5. Greenberg, P., Cox, C., LeBeau, M. M., Fenaux, P., Morel, P. and Sanz, G. (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood, 89, pp. 2079-2088.
6. Raza, A., Qawi, H., Mehdi, M., Mumtaz, M. and Galili, N. (2004) Translational research in myelodysplastic syndromes. Rev Clin Exp Hematol, 8, p. 2.
7. Hofmann, W. K. and Koeffler, H. P. (2002) Important features of myelodysplastic syndrome. Int J Hematol, 76, pp. 222-227.
8. Steensma, D. P. and Tefferi, A. (2003) The myelodysplastic syndrome(s): a perspective and review highlighting current controversies. Leuk Res, 27, pp. 95-120.
9. Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H. and Vijg, J. (2003) Aging and genome maintenance: Lessons from the mouse?. Science, 299, pp. 1355-1359.
10. Capri, M., Salvioli, S., Sevini, F., Valensin, S., Celani, L. and Monti, D. (2006) The genetics of human longevity. Ann N Y Acad Sci, 1067, pp. 252-263.
11. Nisse, C., Haguenoer, J. M., Grandbastien, B., Preudhomme, C., Fontaine, B. and Brillet, J. M. (2001) Occupational and environmental risk factors of the myelodysplastic syndromes in the north of France. Br J Haematol, 112, pp. 927-935.
12. Loft, S. and Poulsen, H. E. (1996) Cancer risk and oxidative DNA damage in man. J Mol Med, 74, pp. 297-312.
13. Hodkinson, C. F., O'Connor, J. M., Alexander, H. D., Bradbury, I., Bonham, M. P. and Hannigan, B. M. (2006) Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: The ZENITH study. J Gerontol A Biol Sci Med Sci, 61, pp. 907-917.
14. Fraga, C. G., Shigenaga, M. K., Park, J. W., Degan, P. and Ames, B. N. (1990) Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci USA, 87, pp. 4533-4537.
15. Farquhar, M. J. and Bowen, D. T. (2003) Oxidative stress and the myelodysplastic syndromes. Int J Hematol, 77, pp. 342-350.
16. Haslberger, A., Varga, F. and Karlic, H. (2006) Recursive causality in evolution: A model for epigenetic mechanisms in cancer development. Med Hypotheses, 67, pp. 1448-1454.
17. Johnson, F. B., Sinclair, D. A. and Guarente, L. (1999) Molecular biology of aging. Cell, 96, pp. 291-302.
18. Kirkwood, T. B. (1977) Evolution of ageing. Nature, 270, pp. 301-304.
19. Extermann, M., Aapro, M., Bernabei, R., Cohen, H. J., Droz, J. P. and Lichtman, S. (2005) Use of comprehensive geriatric assessment in older cancer patients: Recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol, 55, pp. 241-252.
20. Mathers, J. C. (2006) Nutritional modulation of ageing: Genomic and epigenetic approaches. Mech Ageing Dev, 127, pp. 584-589.
21. Panani, A. D. and Roussos, C. (2006) Cytogenetic aspects of adult primary myelodysplastic syndromes: Clinical implications. Cancer Lett, 235, pp. 177-190.
22. Sole, F., Luno, E., Sanzo, C., Espinet, B., Sanz, G. F. and Cervera, J. (2005) Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica, 90, pp. 1168-1178.
23. Haase, D., Steidl, C., Schanz, J., Schabla, R., Pfeilstöcker, M. and Nösslinger, T. (2005) Correlation of cytogenetic findings with morphology, clinical course and prognosis in 2124 patients with MDS. Blood, 106, p. 232.
24. Fenaux, P., Morel, P. and Lai, J. L. (1996) Cytogenetics of myelodysplastic syndromes. Semin Hematol, 33, pp. 127-138.
25. Washington, L. T., Doherty, D., Glassman, A., Martins, J., Ibrahim, S. and Lai, R. (2002) Myeloid disorders with deletion of 5q as the sole karyotypic abnormality: The clinical and pathologic spectrum. Leuk Lymphoma, 43, pp. 761-765.
26. Pierre, R. V. and Hoagland, H. C. (1972) Age-associated aneuploidy: Loss of Y chromosome from human bone marrow cells with aging. Cancer, 30, pp. 889-894.
27. Wiktor, A., Rybicki, B. A., Piao, Z. S., Shurafa, M., Barthel, B. and Maeda, K. (2000) Clinical significance of Y chromosome loss in hematologic disease. Genes Chromosomes Cancer, 27, pp. 11-16.
28. Chen, B., Zhao, W. L., Jin, J., Xue, Y. Q., Cheng, X. and Chen, X. T. (2005) Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries. Leukemia, 19, pp. 767-775.
29. Hofmann, W. K., de Vos, S., Komor, M., Hoelzer, D., Wachsman, W. and Koeffler, H. P. (2002) Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood, 100, pp. 3553-3560.
30. Dewald, G. H., Higgins, R., Griffin, C., Cherry, A. and Rowe, J. (2000) Comparison of interphase FISH and metaphase cytogenetics to study myelodysplasia: An Eastern Cooperative Oncology Group (ECOG) study. Blood, 96, p. 148.
31. Bolufer, P., Barragan, E., Collado, M., Cervera, J., Lopez, J. A. and Sanz, M. A. (2006) Influence of genetic polymorphisms on the risk of developing leukemia and on disease progression. Leuk Res, 30, pp. 1471-1491.
32. Mdo, C Silva, Gaspar, J., Silva, I Duarte, Faber, A. and Rueff, J. (2004) GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes. Environ Mol Mutagen, 43, pp. 258-264.
33. Rund, D., Krichevsky, S., Bar-Cohen, S., Goldschmidt, N., Kedmi, M. and Malik, E. (2005) Therapy-related leukemia: Clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Leukemia, 19, pp. 1919-1928.
34. Wolfler, A., Erkeland, S. J., Bodner, C., Valkhof, M., Renner, W. and Leitner, C. (2005) A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome. Blood, 105, pp. 3731-3736.
35. Balog, A., Borbenyi, Z., Gyulai, Z., Molnar, L. and Mandi, Y. (2005) Clinical importance of transforming growth factor-beta but not of tumor necrosis factor-alpha gene polymorphisms in patients with the myelodysplastic syndrome belonging to the refractory anemia subtype. Pathobiology, 72, pp. 165-170.
36. Gyulai, Z., Balog, A., Borbenyi, Z. and Mandi, Y. (2005) Genetic polymorphisms in patients with myelodysplastic syndrome. Acta Microbiol Immunol Hung, 52, pp. 463-475.
37. Imai, Y., Kurokawa, M., Izutsu, K., Hangaishi, A., Takeuchi, K. and Maki, K. (2000) Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis. Blood, 96, pp. 3154-3160.
38. Shi, X., Shi, W., Song, B., Wan, M. and Bai, S. (2003) A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep, 4, pp. 374-380.
39. Egger, G., Liang, G., Aparicio, A. and Jones, P. A. (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429, pp. 457-463.
40. Aoki, E., Uchida, T., Ohashi, H., Nagai, H., Murase, T. and Ichikawa, A. (2000) Methylation status of the p15INK4B gene in hematopoietic progenitors and peripheral blood cells in myelodysplastic syndromes. Leukemia, 14, pp. 586-593.
41. Uchida, T., Kinoshita, T., Nagai, H., Nakahara, Y., Saito, H. and Hotta, T. (1997) Hypermethylation of the p15INK4B gene in myelodysplastic syndromes. Blood, 90, pp. 1403-1409.
42. Quesnel, B., Guillerm, G., Vereecque, R., Wattel, E., Preudhomme, C. and Bauters, F. (1998) Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and acquired during disease progression. Blood, 91, pp. 2985-2990.
43. Herman, J. G. and Baylin, S. B. (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med, 349, pp. 2042-2054.
44. Lengauer, C., Kinzler, K. W. and Vogelstein, B. (1997) DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci USA, 94, pp. 2545-2550.
45. Pfeilstöcker, M., Karlic, H., Wihlidal, P., Nösslinger, T. and Pittermann, E. (2006) Hypermethylation and reduced carnitine availability - a possible mechanism for downregulation of microsomal carnitine palmitoyltransferase (mCPT) in myelodysplastic syndromes (MDS). Blood, 108, p. 748.
46. Feil, R. (2006) Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res, 600, pp. 46-57.
47. Bender, C. M., Zingg, J. M. and Jones, P. A. (1998) DNA methylation as a target for drug design. Pharm Res, 15, pp. 175-187.
48. Ruter, B., Wijermans, P. W. and Lubbert, M. (2004) DNA methylation as a therapeutic target in hematologic disorders: Recent results in older patients with myelodysplasia and acute myeloid leukemia. Int J Hematol, 80, pp. 128-135.
49. Marciniak, R. and Guarente, L. (2001) Human genetics. Testing telomerase. Nature, 413, pp. 370-371.
50. Ram, R., Uziel, O. and Lahav, M. (2005) The importance of the telomere and telomerase system in hematological malignancies. Leuk Lymphoma, 468, pp. 1121-1135.
51. Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G. and Roskelley, C. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA, 92, pp. 9363-9367.
52. Chang, E. and Harley, C. B. (1995) Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci USA, 92, pp. 11190-11194.
53. Ohyashiki, J. H., Ohyashiki, K., Fujimura, T., Kawakubo, K., Shimamoto, T. and Iwabuchi, A. (1994) Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes. Cancer Res, 54, pp. 3557-3560.
54. Ohyashiki, K., Iwama, H., Yahata, N., Tauchi, T., Kawakubo, K. and Shimamoto, T. (2001) Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation. Leuk Lymphoma, 42, pp. 291-299.
55. Boultwood, J., Fidler, C., Kusec, R., Rack, K., Elliott, P. J. and Atoyebi, O. (1997) Telomere length in myelodysplastic syndromes. Am J Hematol, 56, pp. 266-271.
56. Ohshima, K., Karube, K., Shimazaki, K., Kamma, H., Suzumiya, J. and Hamasaki, M. (2003) Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: Possible role in ineffective hemopoiesis. Leuk Lymphoma, 44, pp. 1339-1346.
57. Shimazaki, K., Ohshima, K., Suzumiya, J., Kawasaki, C. and Kikuchi, M. (2002) Apoptosis and prognostic factors in myelodysplastic syndromes. Leuk Lymphoma, 43, pp. 257-260.
58. Mufti, G. J. (2004) Pathobiology, classification, and diagnosis of myelodysplastic syndrome. Best Pract Res Clin Haematol, 17, pp. 543-557.
59. Gurkan, E., Tanriverdi, K. and Baslamisli, F. (2005) Telomerase activity in myelodysplastic syndromes. Leuk Res, 29, pp. 1131-1139.
60. Holzenberger, M., Kappeler, L. and Filho, C De Magalhaes (2004) IGF-1 signaling and aging. Exp Gerontol, 39, pp. 1761-1764.
61. Shimon, I. and Shpilberg, O. (1995) The insulin-like growth factor system in regulation of normal and malignant hematopoiesis. Leuk Res, 19, pp. 233-240.
62. Xiao, L., Lingyun, W., Ying, T., Yi-Zhi, L. and Shao-Xu, Y. (2006) Expression of type 1 insulin-like growth factor receptor in marrow nucleated cells in malignant hematological disorders: Correlation with apoptosis. Ann Hematol, 85, pp. 95-101.
63. Karlic, H., Lohninger, A., Laschan, C., Lapin, A., Bohmer, F. and Huemer, M. (2003) Downregulation of carnitine acyltransferases and organic cation transporter OCTN2 in mononuclear cells in healthy elderly and patients with myelodysplastic syndromes. J Mol Med, 81, pp. 435-442.
64. Fillitz, M., Karlic, H., Tüchler, H., Zeibig, J., Spiegel, W. and Wihlidal, P. (2006) Does mRNA level of microsomal carnitine palmitoyltransferase predict yield of peripheral blood stem cell apheresis?. Ann Hematol, 85, pp. 386-393.
65. Murphy, E. and Steenbergen, C. (2007) Preconditioning: The mitochondrial connection. Annu Rev Physiol, 69, pp. 51-67.
66. Zhang, C., Liu, V. W., Addessi, C. L., Sheffield, D. A., Linnane, A. W. and Nagley, P. (1998) Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging. Hum Mutat, 11, pp. 360-371.
67. Chinnery, P. F., Samuels, D. C., Elson, J. and Turnbull, D. M. (2002) Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: Is there a common mechanism?. Lancet, 360, pp. 1323-1325.
68. Ogasawara, Y., Nakayama, K., Tarnowka, M., McCoy, J. P., Kajigaya, S. and Levin, B. C. (2005) Mitochondrial DNA spectra of single human CD34+ cells, T cells, B cells, and granulocytes. Blood, 106, pp. 3271-3284.
69. Shin, M. G., Kajigaya, S., Levin, B. C. and Young, N. S. (2003) Mitochondrial DNA mutations in patients with myelodysplastic syndromes. Blood, 101, pp. 3118-3125.
70. Raza, A., Mundle, S., Shetty, V., Alvi, S., Chopra, H. and Span, L. (1996) Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines. Int J Hematol, 63, pp. 265-278.
71. Mundle, S. D., Ali, A., Cartlidge, J. D., Reza, S., Alvi, S. and Showel, M. M. (1999) Evidence for involvement of tumor necrosis factor-alpha in apoptotic death of bone marrow cells in myelodysplastic syndromes. Am J Hematol, 60, pp. 36-47.
72. Sawanobori, M., Yamaguchi, S., Hasegawa, M., Inoue, M., Suzuki, K. and Kamiyama, R. (2003) Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes. Leuk Res, 27, pp. 583-591.
73. Parker, J. E. and Mufti, G. J. (2004) The myelodysplastic syndromes: A matter of life or death. Acta Haematol, 111, pp. 78-99.
74. Ricciardi, M. R., Petrucci, M. T., Gregorj, C., Martini, V., Levi, A. and De Cuia, M. R. (2004) Apoptosis susceptibility and cell-cycle distribution in cells from myelodysplastic syndrome patients: Modulatory in-vitro effects of G-CSF and interferon-alpha. Leuk Lymphoma, 45, pp. 1437-1443.
75. Kalina, U., Hofmann, W. K., Koschmieder, S., Wagner, S., Kauschat, D. and Hoelzer, D. (2000) Alteration of c-mpl-mediated signal transduction in CD34(+) cells from patients with myelodysplastic syndromes. Exp Hematol, 28, pp. 1158-1163.
76. Aguayo, A., Giles, F. and Albitar, M. (2003) Vascularity, angiogenesis and angiogenic factors in leukemias and myelodysplastic syndromes. Leuk Lymphoma, 44, pp. 213-222.
77. Arthur, W. T., Vernon, R. B., Sage, E. H. and Reed, M. J. (1998) Growth factors reverse the impaired sprouting of microvessels from aged mice. Microvasc Res, 55, pp. 260-270.
78. Khorramizadeh, M. R., Tredget, E. E., Telasky, C., Shen, Q. and Ghahary, A. (1999) Aging differentially modulates the expression of collagen and collagenase in dermal fibroblasts. Mol Cell Biochem, 194, pp. 99-108.
79. Hornebeck, W., Emonard, H., Monboisse, J. C. and Bellon, G. (2002) Matrix-directed regulation of pericellular proteolysis and tumor progression. Semin Cancer Biol, 12, pp. 231-241.
80. Stifter, G., Heiss, S., Gastl, G., Tzankov, A. and Stauder, R. (2005) Over-expression of tumor necrosis factor-alpha in bone marrow biopsies from patients with myelodysplastic syndromes: Relationship to anemia and prognosis. Eur J Haematol, 75, pp. 485-491.
81. Cortelezzi, A., Fracchiolla, N. S., Mazzeo, L. M., Silvestris, I., Pomati, M. and Somalvico, F. (2005) Endothelial precursors and mature endothelial cells are increased in the peripheral blood of myelodysplastic syndromes. Leuk Lymphoma, 46, pp. 1345-1351.
82. Morgan, M. A. and Reuter, C. W. (2006) Molecularly targeted therapies in myelodysplastic syndromes and acute myeloid leukemias. Ann Hematol, 85, pp. 139-163.
83. Musto, P. (2004) Thalidomide therapy for myelodysplastic syndromes: current status and future perspectives. Leuk Res, 28, pp. 325-332.
84. List, A., Dewald, G., Bennett, J., Giagounidis, A., Raza, A. and Feldman, E. (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med, 355, pp. 1456-1465.
85. Steinmann, G. G., Klaus, B. and Müller-Hermelink, H. K. (1985) The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand J Immunol, 22, pp. 563-575.
86. Taub, D. D. and Longo, D. L. (2005) Insights into thymic aging and regeneration. Immunol Rev, 205, pp. 72-93.
87. de Vries, E., de Bruin-Versteeg, S., Comans-Bitter, W. M., de Groot, R., Hop, W. C. and Boerma, G. J. (2000) Longitudinal survey of lymphocyte subpopulations in the first year of life. Pediatr Res, 47, pp. 528-557.
88. Paolisso, G., Barbieri, M., Bonafe, M. and Franceschi, C. (2000) Metabolic age modelling: The lesson from centenarians. Eur J Clin Invest, 30, pp. 888-894.
89. Hamblin, T. J. (1996) Immunological abnormalities in myelodysplastic syndromes. Semin Hematol, 33, pp. 150-162.
90. Locatelli, F., Zecca, M., Pession, A., Maserati, E., De Stefano, P. and Severi, F. (1995) Myelodysplastic syndromes: The pediatric point of view. Haematologica, 80, pp. 268-279.
91. Greenberg, P. L., Young, N. S. and Gattermann, N. (2002) Myelodysplastic syndromes. Hematology (Am Soc Hematol Educ Program), pp. 136-161.
92. Thomas, X. and Chelghoum, Y. (2004) Cigarette smoking and acute leukemia. Leuk Lymphoma, 45, pp. 1103-1109.
93. West, R. R., Stafford, D. A., White, A. D., Bowen, D. T. and Padua, R. A. (2000) Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure. Blood, 95, pp. 2093-2097.
94. Bjork, J., Albin, M., Mauritzson, N., Stromberg, U., Johansson, B. and Hagmar, L. (2000) Smoking and myelodysplastic syndromes. Epidemiology, 11, pp. 285-291.
95. Vijg, J. (2000) Somatic mutations and aging: A re-evaluation. Mutat Res, 447, pp. 117-135.
96. Lahmann, C., Bergemann, J., Harrison, G. and Young, A. R. (2001) Matrix metalloproteinase-1 and skin ageing in smokers. Lancet, 357, pp. 935-936.
97. Moraitis, D., De Lorenzo, M. S., Boyle, J. O., Weksler, B. B. and Cohen, E. G. (2005) Levels of cyclooxygenase-2 are increased in the oral mucosa of smokers: Evidence for the role of epidermal growth factor receptor and its ligands. Cancer Res, 65, pp. 664-670.
98. Pedersen-Bjergaard, J., Andersen, M. K. and Christiansen, D. H. (2000) Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood, 95, pp. 3273-3279.
99. Pedersen-Bjergaard, J., Pedersen, M., Roulston, D. and Philip, P. (1995) Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood, 86, pp. 3542-3552.
100. Krishnan, A., Bhatia, S., Slovak, M. L., Arber, D. A., Niland, J. C. and Nademanee, A. (2000) Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: An assessment of risk factors. Blood, 95, pp. 1588-1593.
101. Tester, W. J., Kinsella, T. J., Waller, B., Makuch, R. W., Kelley, P. A. and Glatstein, E. (1984) Second malignant neoplasms complicating Hodgkin's disease: The National Cancer Institute experience. J Clin Oncol, 2, pp. 762-769.
102. Leone, G., Mele, L., Pulsoni, A., Equitani, F. and Pagano, L. (1999) The incidence of secondary leukemias. Haematologica, 84, pp. 937-945.
103. Cabantchik, Z. I., Breuer, W., Zanninelli, G. and Cianciulli, P. (2005) LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol, 18, pp. 277-287.
104. Strom, S. S., Gruschkus, S. K., Pierce, S. A. and Estey, E. H. (2005) Risk factors of myelodysplastic syndromes: A case-control study. Leukemia, 19, pp. 1912-1918.
105. Yoshida, K., Hirabayashi, Y., Watanabe, F., Sado, T. and Inoue, T. (2006) Caloric restriction prevents radiation-induced myeloid leukemia in C3H/HeMs mice and inversely increases incidence of tumor-free death: implications in changes in number of hemopoietic progenitor cells. Exp Hematol, 34, pp. 274-283.
106. Morel, P., Declercq, C., Hebbar, M., Bauters, F. and Fenaux, P. (1996) Prognostic factors in myelodysplastic syndromes: Critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques. Br J Haematol, 94, pp. 116-119.
107. Kuendgen, A., Strupp, C., Aivado, M., Hildebrandt, B., Haas, R. and Gattermann, N. (2006) Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol, 34, pp. 5358-5365.
108. Nösslinger, T., Tüchler, H., Germing, U., Valent, P., Krieger, O. and Haase, D. (2006) Individualizing IPSS risk assessment in myelodysplastic syndromes by additionally taking into account age, gender and French-American-British (FAB) classification. Blood, 108, p. 739.
109. Aul, C., Gattermann, N., Heyll, A., Germing, U., Derigs, G. and Schneider, W. (1992) Primary myelodysplastic syndromes: Analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia, 6, pp. 52-59.
110. Mufti, G. J., Stevens, J. R., Oscier, D. G., Hamblin, T. J. and Machin, D. (1985) Myelodysplastic syndromes: A scoring system with prognostic significance. Br J Haematol, 59, pp. 425-443.
111. Malcovati, L., Porta, M. G., Pascutto, C., Invernizzi, R., Boni, M. and Travaglino, E. (2005) Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: A basis for clinical decision making. J Clin Oncol, 23, pp. 7594-7603.
112. Sanz, G. F., Sanz, M. A., Vallespi, T., Canizo, M. C., Torrabadella, M. and Garcia, S. (1989) Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood, 74, pp. 395-408.
113. Desole, S. S., Lussar, M., Pirhofer, U., Holzner, C., Kemmler, B. and Sperner-Unterweger, G. (2006) Geriatric assessment of tumor patients in Austria. Onkologie, 29, p. 221.
114. Aul, C., Bowen, D. T. and Yoshida, Y. (1998) Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica, 83, pp. 71-86.
115. Rosenfeld, C. and List, A. (2000) A hypothesis for the pathogenesis of myelodysplastic syndromes: Implications for new therapies. Leukemia, 14, pp. 2-8.
116. Agrelo, R., Cheng, W. H., Setien, F., Ropero, S., Espada, J. and Fraga, M. F. (2006) Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci USA, 103, pp. 8822-8827.
117. Cherian, S. and Bagg, A. (2006) The genetics of the myelodysplastic syndromes: Classical cytogenetics and recent molecular insights. Hematology, 11, pp. 1-13.
118. Rudolph, K. L., Chang, S., Lee, H. W., Blasco, M., Gottlieb, G. J. and Greider, C. (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell, 96, pp. 701-712.
119. Chen, Z. (2002) Telomerase activity in myelodysplastic syndrome. Chin Med J, 115, pp. 1475-1478.
120. Claessens, Y. E., Bouscary, D., Dupont, J. M., Picard, F., Melle, J. and Gisselbrecht, S. (2002) In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood, 99, pp. 1594-1601.
121. Razzaque, M. S. and Lanske, B. (2006) Hypervitaminosis D and premature aging: Lessons learned from Fgf23 and Klotho mutant mice. Trends Mol Med, 12, pp. 298-305.
122. Mellibovsky, L., Diez, A., Serrano, S., Aubia, J., Perez-Vila, E. and Marinoso, M. L. (1996) Bone remodeling alterations in myelodysplastic syndrome. Bone, 19, pp. 401-405.
123. Xie, G., Bai, R., Wang, Y. and Zhu, P. (1998) Semi-quantitative study of calcitonin gene methylation in myelodysplastic syndrome. Chin Med J, 111, pp. 690-693.
124. Vidal, D. O., Paixao, V. A., Brait, M., Souto, E. X., Caballero, O. L. and Lopes, L. F. (2007) Aberrant methylation in pediatric myelodysplastic syndrome. Leuk Res, 31, pp. 175-181.