Myelodysplastic syndromes: Review of pathophysiology and current novel treatment approaches

Current Cancer Drug Targets

Volumn 7, Issue 6, 2007, Pages 541-558

  Warlick, E D ^a   Smith, B D ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Bone marrow transplantation; Differentiation therapy; Epigenetic therapy; Immunomodulation; Myelodysplastic syndrome; Pathophysiology

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ALEMTUZUMAB; ARSENIC TRIOXIDE; AZACITIDINE; BENZENE; BORTEZOMIB; CYCLOSPORIN A; CYTARABINE; DNA METHYLTRANSFERASE INHIBITOR; ETANERCEPT; ETOPOSIDE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HISTONE DEACETYLASE INHIBITOR; INFLIXIMAB; LENALIDOMIDE; LONAFARNIB; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; PLACEBO; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RETINOIC ACID; SCIO 469; SORAFENIB; THALIDOMIDE; THYMOCYTE ANTIBODY; TRANSCRIPTION FACTOR GATA 1; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VALPROIC ACID; VATALANIB;

ACUTE GRANULOCYTIC LEUKEMIA; ANGIOGENESIS; BLEEDING; BONE MARROW TRANSPLANTATION; CHROMOSOME ABERRATION; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CYTOGENETICS; CYTOPENIA; DISEASE CLASSIFICATION; DISEASE COURSE; DNA DAMAGE; DNA REPLICATION; DRUG MECHANISM; ENVIRONMENTAL EXPOSURE; ENZYME INHIBITION; EPIGENETICS; GENE EXPRESSION; HUMAN; IMMUNE DYSREGULATION; IMMUNOMODULATION; INFECTION; LEUKEMIA; MONOTHERAPY; MUTATION; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; ONCOGENE RAS; PROGNOSIS; REVIEW; SCORING SYSTEM; STEM CELL TRANSPLANTATION; THROMBOCYTOPENIA; TREATMENT PLANNING; TRISOMY 8;

CHROMOSOME ABERRATIONS; EPIGENESIS, GENETIC; HUMANS; MYELODYSPLASTIC SYNDROMES;

EID: 34548453718     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800907781662284     Document Type: Review

References (219)

1. Aul, C.; Giagounidis, U.; Germing, U. Epidemiological features of myelodysplastic syndrome: real or factitious? Int. J. Hematol. 2001, 73(4), 405-410.
2. Yin, S. N.; Hayes, R. B.; Linet, M. S.; Li, G. L.; Dosemeci, M.; Travis, L. B.; Li, C. Y.; Zhang, Z. N.; Li, D. G.; Chow, W. H.; Wacholder, S.; Wang, Y. Z.; Jiang, Z. L.; Dai, T. R.; Zhang, W. Y.; Chao, X. J.; Ye, P. Z.; Kou, Q. R.; Zhang, X. C.; Lin, X. F.; Meng, J. F.; Ding, C. Y.; Zho, J. S.; Blot, W. J. A cohort study of cancer among benzene-exposed workers in China: overall results. Am. J. Ind. Med. 1996, 29(3), 227-235.
3. West, R. R.; Stafford, D. A.; Farrow, A.; Jacobs, A. Occupational and environmental exposures and myelodysplasia: a case-control study. Leuk. Res. 1995, 19(2), 127-139.
4. Moloney, W. C. Radiogenic leukemia revisited. Blood 1987, 70(4), 905-908.
5. Pedersen-Bjergaard, J.; Philip, P.; Larsen, S. O.; Andersson, M.; Daugaard, G.; Ersboll, J.; Hansen, S. W.; Hou-Jensen, K.; Nielsen, D.; Sigsgaard, T. C. Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series. Leukemia 1993, 7(12), 1975-1986.
6. Pasqualetti, P.; Festuccia, V.; Acitelli, P.; Collacciani, A.; Giusti, A.; Casale, R. Tobacco smoking and risk of haematological malignancies in adults: a case-control study. Br. J. Haematol. 1997, 97(3), 659-662.
7. Ido, M.; Nagata, C.; Kawakami, N.; Shimizu, H.; Yoshida, Y.; Nomura, T.; Mizoguchi, H. A case-control study of myelodysplastic syndromes among Japanese men and women. Leuk. Res. 1996, 20(9), 727-731.
8. Mundle, S.; Allampallam, K.; Aftab, R. K.; Dangerfield, B.; Cartlidge, J.; Zeitler, D.; Afenya, E.; Alvi, S.; Shetty, V.; Venugopal, P.; Raza, A. Presence of activation-related m-RNA for EBV and CMV in the bone marrow of patients with myelodysplastic syndromes. Cancer Lett. 2001, 164(2), 197-205.
9. Dalamaga, M.; Petridou, E.; Cook, F. E.; Trichopoulos, D. Risk factors for myelodysplastic syndromes: a case-control study in Greece. Cancer Causes Control. 2002, 13(7), 603-608.
10. Rund, D.; Ben Yehuda, D. Therapy-related leukemia and myelodysplasia: evolving concepts of pathogenesis and treatment. Hematology 2004, 9(3), 179-187.
11. Olney, H. J.; Le Beau, M. M. The cytogenetics of myelodysplastic syndromes. Best. Pract. Res. Clin. Haematol. 2001, 14(3), 479-495.
12. Parker, J. E.; Mufti, G. J.; Rasool, F.; Mijovic, A.; Devereux, S.; Pagliuca, A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood 2000, 96(12), 3932-3938.
13. Rajapaksa, R.; Ginzton, N.; Rott, L. S.; Greenberg, P. L. Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. Blood 1996, 88(11), 4275-4287.
14. Parker, J. E.; Mufti, G. J. Ineffective haemopoiesis and apoptosis in myelodysplastic syndromes. Br. J. Haematol. 1998, 101(2), 220-230.
15. Rosenfeld, C.; List, A. A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies. Leukemia 2000, 14(1), 2-8.
16. Bennett, J. M.; Catovsky, D.; Daniel, M. T.; Flandrin, G.; Galton, D. A.; Gralnick, H. R.; Sultan, C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br. J. Haematol. 1976, 33(4), 451-458.
17. Bennett, J. M.; Catovsky, D.; Daniel, M. T.; Flandrin, G.; Galton, D. A.; Gralnick, H. R.; Sultan, C. Proposals for the classification of the myelodysplastic syndromes. Br. J. Haematol. 1982, 51(2), 189-199.
18. Steensma, D. P.; Tefferi, A. The myelodysplastic syndrome(s): a perspective and review highlighting current controversies. Leuk. Res. 2003, 27(2), 95-120.
19. Steensma, D. P.; Bennett, J. M. The myelodysplastic syndromes: diagnosis and treatment. Mayo Clin. Proc. 2006, 81(1), 104-130.
20. Harris, N. L.; Jaffe, E. S.; Diebold, J.; Flandrin, G.; Muller-Hermelink, H. K.; Vardiman, J.; Lister, T. A.; Bloomfield, C. D. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J. Clin. Oncol. 1999, 17(12), 3835-3849.
21. Vardiman, J. W.; Harris, N. L.; Brunning, R. D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002, 100(7), 2292-2302.
22. Greenberg, P.; Cox, C.; LeBeau, M. M.; Fenaux, P.; Morel, P.; Sanz, G.; Sanz, M.; Vallespi, T.; Hamblin, T.; Oscier, D.; Ohyashiki, K.; Toyama, K.; Aul, C.; Mufti, G.; Bennett, J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997, 89(6), 2079-2088.
23. Catenacci, D. V.; Schiller, G. J. Myelodysplasic syndromes: A comprehensive review. Blood Rev. 2005, 19(6), 301-319.
24. Mufti, G. J. Pathobiology, classification, and diagnosis of myelodysplastic syndrome. Best. Pract. Res. Clin. Haematol. 2004, 17(4), 543-557.
25. Kuang, S.; Liang, W. Clinical analysis of 43 cases of chronic benzene poisoning. Chem. Biol. Interact. 2005, 153-154, 129-135.
26. Aksoy, M.; Dincol, K.; Erdem, S.; Dincol, G. Acute leukemia due to chronic exposure to benzene. Am. J. Med. 1972, 52(2), 160-166.
27. Yardley-Jones, A.; Anderson, D.; Parke, D. V. The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. Br. J. Ind. Med. 1991, 48(7), 437-444.
28. Hiraku, Y.; Kawanishi, S. Oxidative DNA damage and apoptosis induced by benzene metabolites. Cancer Res. 1996, 56(22), 5172-5178.
29. Smith, M. T. The mechanism of benzene-induced leukemia: a hypothesis and speculations on the causes of leukemia. Environ. Health Perspect. 1996, 104(Suppl. 6), 1219-1225.
30. Rothman, N.; Haas, R.; Hayes, R. B.; Li, G. L.; Wiemels, J.; Campleman, S.; Quintana, P. J.; Xi, L. J.; Dosemeci, M.; Titenko-Holland, N. Benzene induces gene-duplicating but not gene-inactivating mutations at the glycophorin A locus in exposed humans. Proc. Natl. Acad. Sci. USA 1995, 92(9), 4069-4073.
31. Aul, C.; Bowen, D. T.; Yoshida, Y. Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica 1998, 83(1), 71-86.
32. Pedersen-Bjergaard, J.; Andersen, M. K.; Christiansen, D. H.; Nerlov, C. Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood 2002, 99(6), 1909-1912.
33. Matsuo, T.; Tomonaga, M.; Bennett, J. M.; Kuriyama, K.; Imanaka, F.; Kuramoto, A.; Kamada, N.; Ichimaru, M.; Finch, S. C.; Pisciotta, A. V. Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia. Jpn. J. Clin. Oncol. 1988, 18(2), 91-96.
34. Kadhim, M. A.; Lorimore, S. A.; Hepburn, M. D.; Goodhead, D. T.; Buckle, V. J.; Wright, E. G. Alpha-particle-induced chromosomal instability in human bone marrow cells. Lancet 1994, 344(8928), 987-988.
35. Kitagawa, M.; Yamaguchi, S.; Takahashi, M.; Tanizawa, T.; Hirokawa, K.; Kamiyama, R. Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia. Leukemia 1998, 12(4), 486-492.
36. Ogawa, T.; Kitagawa, M.; Hirokawa, K. Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages. Mech. Ageing Dev. 2000, 117(1-3), 57-68.
37. Sawanobori, M.; Yamaguchi, S.; Hasegawa, M.; Inoue, M.; Suzuki, K.; Kamiyama, R.; Hirokawa, K.; Kitagawa, M. Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes. Leuk. Res. 2003, 27(7), 583-591.
38. Moyzis, R. K.; Buckingham, J. M.; Cram, L. S.; Dani, M.; Deaven, L. L.; Jones, M. D.; Meyne, J.; Ratliff, R. L.; Wu, J. R. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA 1988, 85(18), 6622-6626.
39. Iwama, H.; Ohyashiki, K.; Ohyashiki, J. H.; Hayashi, S.; Yahata, N.; Ando, K.; Toyama, K.; Hoshika, A.; Takasaki, M.; Mori, M.; Shay, J. W. Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum. Genet. 1998, 102(4), 397-402.
40. Allsopp, R. C.; Vaziri, H.; Patterson, C.; Goldstein, S.; Younglai, E. V.; Futcher, A. B.; Greider, C. W.; Harley, C. B. Telomere length predicts replicative capacity of human fibroblasts. Proc. Natl. Acad. Sci. USA 1992, 89(21), 10114-10118.
41. Kim, N. W.; Piatyszek, M. A.; Prowse, K. R.; Harley, C. B.; West, M. D.; Ho, P. L.; Coviello, G. M.; Wright, W. E.; Weinrich, S. L.; Shay, J. W. Specific association of human telomerase activity with immortal cells and cancer. Science 1994, 266(5193), 2011-2015.
42. Shay, J. W.; Bacchetti, S. A survey of telomerase activity in human cancer. Eur. J. Cancer 1997, 33(5), 787-791.
43. Engelhardt, M.; Kumar, R.; Albanell, J.; Pettengell, R.; Han, W.; Moore, M. A. Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. Blood 1997, 90(1), 182-193.
44. Ohyashiki, J. H.; Iwama, H.; Yahata, N.; Ando, K.; Hayashi, S.; Shay, J. W.; Ohyashiki, K. Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. Clin. Cancer Res. 1999, 5(5), 1155-1160.
45. Hirai, H. Molecular mechanisms of myelodysplastic syndrome. Jpn. J. Clin. Oncol. 2003, 33(4), 153-160.
46. Look, A. T. Molecular Pathogenesis of MDS. Hematology (Am. Soc. Hematol. Educ. Program) 2005, 156-160.
47. Nimer, S. D. Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q. J. Clin. Oncol. 2006, 24(16), 2576-2582.
48. Jary, L.; Mossafa, H.; Fourcade, C.; Genet, P.; Pulik, M.; Flandrin, G. The 17p-syndrome: a distinct myelodysplastic syndrome entity? Leuk. Lymphoma 1997, 25(1-2), 163-168.
49. Paulsson, K.; Johansson, B. Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes. Pathol. Biol. (Paris) 2007, 55(1), 37-48.
50. Boultwood, J.; Lewis, S.; Wainscoat, J. S. The 5q-syndrome. Blood 1994, 84(10), 3253-3260.
51. Nimer, S. D.; Golde, D. W. The 5q- abnormality. Blood 1987, 70(6), 1705-1712.
52. Fairman, J.; Chumakov, I.; Chinault, A. C.; Nowell, P. C.; Nagarajan, L. Physical mapping of the minimal region of loss in 5q- chromosome. Proc. Natl. Acad. Sci. USA 1995, 92(16), 7406-7410.
53. Zhao, N.; Stoffel, A.; Wang, P. W.; Eisenbart, J. D.; Espinosa, R., III; Larson, R. A.; Le Beau, M. M. Molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases to 1-1.5 Mb and preparation of a PAC-based physical map. Proc. Natl. Acad. Sci. USA 1997, 94(13), 6948-6953.
54. Jaju, R. J.; Boultwood, J.; Oliver, F. J.; Kostrzewa, M.; Fidler, C.; Parker, N.; McPherson, J. D.; Morris, S. W.; Muller, U.; Wainscoat, J. S.; Kearney, L. Molecular cytogenetic delineation of the critical deleted region in the 5q-syndrome. Genes Chromosomes Cancer 1998, 22(3), 251-256.
55. Horrigan, S. K.; Arbieva, Z. H.; Xie, H. Y.; Kravarusic, J.; Fulton, N. C.; Naik, H.; Le, T. T.; Westbrook, C. A. Delineation of a minimal interval and identification of 9 candidates for a tumor suppressor gene in malignant myeloid disorders on 5q31. Blood 2000, 95(7), 2372-2377.
56. Le Beau, M. M.; Espinosa, R., III; Neuman, W. L.; Stock, W.; Roulston, D.; Larson, R. A.; Keinanen, M.; Westbrook, C. A. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. Proc. Natl. Acad. Sci. USA 1993, 90(12), 5484-5488.
57. Boultwood, J.; Fidler, C.; Strickson, A. J.; Watkins, F.; Kostrzewa, M.; Jaju, R. J.; Muller, U.; Wainscoat, J. S. Transcription mapping of the 5q-syndrome critical region: cloning of two novel genes and sequencing, expression, and mapping of a further six novel cDNAs. Genomics 2000, 66(1), 26-34.
58. Vallespi, T.; Imbert, M.; Mecucci, C.; Preudhomme, C.; Fenaux, P. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica 1998, 83(3), 258-275.
59. Wattel, E.; Lai, J. L.; Hebbar, M.; Preudhomme, C.; Grahek, D.; Morel, P.; Bauters, F.; Fenaux, P. De novo myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 20: a subtype of MDS with distinct hematological and prognostic features? Leuk. Res. 1993, 17(11), 921-926.
60. Davis, M. P.; Dewald, G. W.; Pierre, R. V.; Hoagland, H. C. Hematologic manifestations associated with deletions of the long arm of chromosome 20. Cancer Genet. Cytogenet. 1984, 12(1), 63-71.
61. Asimakopoulos, F. A.; Green, A. R. Deletions of chromosome 20q and the pathogenesis of myeloproliferative disorders. Br. J. Haematol. 1996, 95(2), 219-226.
62. Liang, H.; Fairman, J.; Claxton, D. F.; Nowell, P. C.; Green, E. D.; Nagarajan, L. Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: evidence for multiple critical loci. Proc. Natl. Acad. Sci. USA 1998, 95(7), 3781-3785.
63. Pasquali, F.; Bernasconi, P.; Casalone, R.; Fraccaro, M.; Bernasconi, C.; Lazzarino, M.; Morra, E.; Alessandrino, E. P.; Marchi, M. A.; Sanger, R. Pathogenetic significance of "pure" monosomy 7 in myeloproliferative disorders. Analysis of 14 cases. Hum. Genet. 1982, 62(1), 40-51.
64. Le Beau, M. M.; Espinosa, R., III; Davis, E. M.; Eisenbart, J. D.; Larson, R. A.; Green, E. D. Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases. Blood 1996, 88(6), 1930-1935.
65. Merlat, A.; Lai, J. L.; Sterkers, Y.; Demory, J. L.; Bauters, F.; Preudhomme, C.; Fenaux, P. Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion. A report on 25 cases. Leukemia 1999, 13(2), 250-257.
66. Albin, M.; Bjork, J.; Welinder, H.; Tinnerberg, H.; Mauritzson, N.; Johansson, B.; Billstrom, R.; Stromberg, U.; Mikoczy, Z.; Ahlgren, T.; Nilsson, P. G.; Mitelman, F.; Hagmar, L. Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents. Scand. J. Work Environ. Health 2000, 26(6), 482-491.
67. Thirman, M. J.; Larson, R. A. Therapy-related myeloid leukemia. Hematol. Oncol. Clin. North Am. 1996, 10(2), 293-320.
68. Wiederschain, D.; Kawai, H.; Shilatifard, A.; Yuan, Z. M. Multiple mixed lineage leukemia (MLL) fusion proteins suppress p53-mediated response to DNA damage. J. Biol. Chem. 2005, 280(26), 24315-24321.
69. Papenhausen, P. R.; Griffin, S.; Tepperberg, J. Oncogene amplification in transforming myelodysplasia. Exp. Mol. Pathol. 2005, 79(2), 168-175.
70. Poppe, B.; Vandesompele, J.; Schoch, C.; Lindvall, C.; Mrozek, K.; Bloomfield, C. D.; Beverloo, H. B.; Michaux, L.; Dastugue, N.; Herens, C.; Yigit, N.; De Paepe, A.; Hagemeijer, A.; Speleman, F. Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies. Blood 2004, 103(1), 229-235.
71. Pappa, V.; Young, B. D.; Economopoulos, T.; Papageorgiou, E.; Panani, A.; Lilington, D.; Bollas, G.; Stamouli, M.; Kontsioti, F.; Tsiotra, P.; Vessalas, G.; Dervenoulas, J.; Raptis, S. Absence of MLL gene rearrangement in de novo myelodysplastic syndromes (MDS). Ann. Hematol. 2004, 83(3), 170-175.
72. Paquette, R. L.; Landaw, E. M.; Pierre, R. V.; Kahan, J.; Lubbert, M.; Lazcano, O.; Isaac, G.; McCormick, F.; Koeffler, H. P. N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood 1993, 82(2), 590-599.
73. Bos, J. L. ras oncogenes in human cancer: a review. Cancer Res. 1989, 49(17), 4682-4689.
74. Harris, C. C.; Hollstein, M. Clinical implications of the p53 tumorsuppressor gene. N. Engl. J. Med. 1993, 329(18), 1318-1327.
75. Lai, J. L.; Preudhomme, C.; Zandecki, M.; Flactif, M.; Vanrumbeke, M.; Lepelley, P.; Wattel, E.; Fenaux, P. Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia 1995, 9(3), 370-381.
76. Horiike, S.; Kita-Sasai, Y.; Nakao, M.; Taniwaki, M. Configuration of the TP53 gene as an independent prognostic parameter of myelodysplastic syndrome. Leuk. Lymphoma 2003, 44(6), 915-922.
77. Wattel, E.; Preudhomme, C.; Hecquet, B.; Vanrumbeke, M.; Quesnel, B.; Dervite, I.; Morel, P.; Fenaux, P. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 1994, 84(9), 3148-3157.
78. Paulsson, K.; Heidenblad, M.; Strombeck, B.; Staaf, J.; Jonsson, G.; Borg, A.; Fioretos, T.; Johansson, B. High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration. Leukemia 2006, 20(5), 840-846.
79. Verdorfer, I.; Brecevic, L.; Saul, W.; Schenker, B.; Kirsch, M.; Trautmann, U.; Helm, G.; Gramatzki, M.; Gebhart, E. Comparative genomic hybridization-aided unraveling of complex karyotypes in human hematopoietic neoplasias. Cancer Genet. Cytogenet. 2001, 124(1), 1-6.
80. Wilkens, L.; Tchinda, J.; Burkhardt, D.; Nolte, M.; Werner, M.; Georgii, A. Analysis of hematologic diseases using conventional karyotyping, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). Hum. Pathol. 1998, 29(8), 833-839.
81. Babicz, M.; Kowalczyk, J. R.; Winnicka, D.; Gaworczyk, A.; Lejman, M.; Dmowski, R.; Kaczanowska, K. The effectiveness of high-resolution-comparative genomic hybridization in detecting the most common chromosomal abnormalities in pediatric myelodysplastic syndromes. Cancer Genet. Cytogenet. 2005, 158(1), 49-54.
82. Wilkens, L.; Burkhardt, D.; Tchinda, J.; Busche, G.; Werner, M.; Nolte, M.; Ganser, A.; Georgii, A. Cytogenetic aberrations in myelodysplastic syndrome detected by comparative genomic hybridization and fluorescence in situ hybridization. Diagn. Mol. Pathol. 1999, 8(1), 47-53.
83. Wolfler, A.; Erkeland, S. J.; Bodner, C.; Valkhof, M.; Renner, W.; Leitner, C.; Olipitz, W.; Pfeilstocker, M.; Tinchon, C.; Emberger, W.; Linkesch, W.; Touw, I. P.; Sill, H. A functional single-nucleotide polymorphism of the GCSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome. Blood 2005, 105(9), 3731-3736.
84. Willman, C. L. Molecular genetic features of myelodysplastic syndromes (MDS). Leukemia 1998, 12(Suppl. 1), S2-S6.
85. Chen, H.; Sandler, D. P.; Taylor, J. A.; Shore, D. L.; Liu, E.; Bloomfield, C. D.; Bell, D. A. Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 1996, 347(8997), 295-297.
86. Rothman, N.; Smith, M. T.; Hayes, R. B.; Traver, R. D.; Hoener, B.; Campleman, S.; Li, G. L.; Dosemeci, M.; Linet, M.; Zhang, L.; Xi, L.; Wacholder, S.; Lu, W.; Meyer, K. B.; Titenko-Holland, N.; Stewart, J. T.; Yin, S.; Ross, D. Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C->T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res. 1997, 57(14), 2839-2842.
87. Naoe, T.; Takeyama, K.; Yokozawa, T.; Kiyoi, H.; Seto, M.; Uike, N.; Ino, T.; Utsunomiya, A.; Maruta, A.; Jin-nai, I.; Kamada, N.; Kubota, Y.; Nakamura, H.; Shimazaki, C.; Horiike, S.; Kodera, Y.; Saito, H.; Ueda, R.; Wiemels, J.; Ohno, R. Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia. Clin. Cancer Res. 2000, 6(10), 4091-4095.
88. Olipitz, W.; Hopfinger, G.; Aguiar, R. C.; Gunsilius, E.; Girschikofsky, M.; Bodner, C.; Hiden, K.; Linkesch, W.; Hoefler, G.; Sill, H. Defective DNA-mismatch repair: a potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia. Genes Chromosomes Cancer 2002, 34(2), 243-248.
89. Robertson, K. D.; Jones, P. A. DNA methylation: past, present and future directions. Carcinogenesis 2000, 21(3), 461-467.
90. Singal, R.; Ginder, G. D. DNA methylation. Blood 1999, 93(12), 4059-4070.
91. Herman, J. G.; Civin, C. I.; Issa, J. P.; Collector, M. I.; Sharkis, S. J.; Baylin, S. B. Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. Cancer Res. 1997, 57(5), 837-841.
92. Quesnel, B.; Guillerm, G.; Vereecque, R.; Wattel, E.; Preudhomme, C.; Bauters, F.; Vanrumbeke, M.; Fenaux, P. Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and acquired during disease progression. Blood 1998, 91(8), 2985-2990.
93. Leone, G.; Teofili, L.; Voso, M. T.; Lubbert, M. DNA methylation and demethylating drugs in myelodysplastic syndromes and secondary leukemias. Haematologica 2002, 87(12), 1324-1341.
94. Aggerholm, A.; Holm, M. S.; Guldberg, P.; Olesen, L. H.; Hokland, P. Promoter hypermethylation of p15INK4B, HIC1, CDH1, and ER is frequent in myelodysplastic syndrome and predicts poor prognosis in early-stage patients. Eur. J. Haematol. 2006, 76(1), 23-32.
95. Christiansen, D. H.; Andersen, M. K.; Pedersen-Bjergaard, J. Methylation of p15INK4B is common, is associated with deletion of genes on chromosome arm 7q and predicts a poor prognosis in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2003, 17(9), 1813-1819.
96. Dhodapkar, M.; Grill, J.; Lust, J. A. Abnormal regional hypermethylation of the calcitonin gene in myelodysplastic syndromes. Leuk. Res. 1995, 19(10), 719-726.
97. Wu, S.; Xie, G.; Bai, R.; Wang, Y.; Zhu, P. Semi-quantitative study of calcitonin gene methylation in myelodysplastic syndrome. Chin. Med. J. (Engl.) 1998, 111(8), 690-693.
98. Bai, R.; Wu, S.; Zhu, P.; Xue, H.; Xu, Y.; Qin, X. Quantitative study of calcitonin gene methylation in myelodysplastic syndromes. Zhonghua Xue. Ye. Xue. Za Zhi. 1997, 18(1), 17-20.
99. Li, G.; Zou, D.; Bai, R. Clinical significance of human calcitonin and gene-related peptide in the serum of myelodysplastic syndromes patients. Zhonghua Xue. Ye. Xue. Za Zhi. 1999, 20(2), 79-81.
100. Marks, P.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer 2001, 1(3), 194-202.
101. Haggarty, S. J.; Koeller, K. M.; Wong, J. C.; Grozinger, C. M.; Schreiber, S. L. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc. Natl. Acad. Sci. USA 2003, 100(8), 4389-4394.
102. Wolf, D.; Rodova, M.; Miska, E. A.; Calvet, J. P.; Kouzarides, T. Acetylation of beta-catenin by CREB-binding protein (CBP). J. Biol. Chem. 2002, 277(28), 25562-25567.
103. Bannister, A. J.; Miska, E. A.; Gorlich, D.; Kouzarides, T. Acetylation of importin-alpha nuclear import factors by CBP/p300. Curr. Biol. 2000, 10(8), 467-470.
104. Cohen, H. Y.; Lavu, S.; Bitterman, K. J.; Hekking, B.; Imahiyerobo, T. A.; Miller, C.; Frye, R.; Ploegh, H.; Kessler, B. M.; Sinclair, D. A. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol. Cell 2004, 13(5), 627-638.
105. Fuino, L.; Bali, P.; Wittmann, S.; Donapaty, S.; Guo, F.; Yamaguchi, H.; Wang, H. G.; Atadja, P.; Bhalla, K. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol. Cancer Ther. 2003, 2(10), 971-984.
106. Morgan, M. A.; Reuter, C. W. Molecularly targeted therapies in myelodysplastic syndromes and acute myeloid leukemias. Ann. Hematol. 2006, 85(3), 139-163.
107. Johnstone, R. W.; Licht, J. D. Histone deacetylase inhibitors in cancer therapy: is transcription the primary target? Cancer Cell 2003, 4(1), 13-18.
108. Kitagawa, M.; Saito, I.; Kuwata, T.; Yoshida, S.; Yamaguchi, S.; Takahashi, M.; Tanizawa, T.; Kamiyama, R.; Hirokawa, K. Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes. Leukemia 1997, 11(12), 2049-2054.
109. Stifter, G.; Heiss, S.; Gastl, G.; Tzankov, A.; Stauder, R. Over-expression of tumor necrosis factor-alpha in bone marrow biopsies from patients with myelodysplastic syndromes: relationship to anemia and prognosis. Eur. J. Haematol. 2005, 75(6), 485-491.
110. Shetty, V.; Mundle, S.; Alvi, S.; Showel, M.; Broady-Robinson, L.; Dar, S.; Borok, R.; Showel, J.; Gregory, S.; Rifkin, S.; Gezer, S.; Parcharidou, A.; Venugopal, P.; Shah, R.; Hernandez, B.; Klein, M.; Alston, D.; Robin, E.; Dominquez, C.; Raza, A. Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes. Leuk. Res. 1996, 20(11-12), 891-900.
111. Raza, A.; Mundle, S.; Shetty, V.; Alvi, S.; Chopra, H.; Span, L.; Parcharidou, A.; Dar, S.; Venugopal, P.; Borok, R.; Gezer, S.; Showel, J.; Loew, J.; Robin, E.; Rifkin, S.; Alston, D.; Hernandez, B.; Shah, R.; Kaizer, H.; Gregory, S. Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines. Int. J. Hematol. 1996, 63(4), 265-278.
112. Hsu, H.; Xiong, J.; Goeddel, D. V. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 1995, 81(4), 495-504.
113. Hsu, H.; Huang, J.; Shu, H. B.; Baichwal, V.; Goeddel, D. V. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 1996, 4(4), 387-396.
114. Flores-Figueroa, E.; Gutierrez-Espindola, G.; Montesinos, J. J.; Arana-Trejo, R. M.; Mayani, H. In vitro characterization of hematopoietic microenvironment cells from patients with myelodysplastic syndrome. Leuk. Res. 2002, 26(7), 677-686.
115. Wetzler, M.; Kurzrock, R.; Estrov, Z.; Estey, E.; Talpaz, M. Cytokine expression in adherent layers from patients with myelodysplastic syndrome and acute myelogenous leukemia. Leuk. Res. 1995, 19(1), 23-34.
116. Deeg, H. J.; Beckham, C.; Loken, M. R.; Bryant, E.; Lesnikova, M.; Shulman, H. M.; Gooley, T. Negative regulators of hemopoiesis and stroma function in patients with myelodysplastic syndrome. Leuk. Lymphoma 2000, 37(3-4), 405-414.
117. Koike, M.; Ishiyama, T.; Tomoyasu, S.; Tsuruoka, N. Spontaneous cytokine overproduction by peripheral blood mononuclear cells from patients with myelodysplastic syndromes and aplastic anemia. Leuk. Res. 1995, 19(9), 639-644.
118. Bouscary, D.; De Vos, J.; Guesnu, M.; Jondeau, K.; Viguier, F.; Melle, J.; Picard, F.; Dreyfus, F.; Fontenay-Roupie, M. Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia 1997, 11(6), 839-845.
119. Gersuk, G. M.; Lee, J. W.; Beckham, C. A.; Anderson, J.; Deeg, H. J. Fas (CD95) receptor and Fas-ligand expression in bone marrow cells from patients with myelodysplastic syndrome. Blood 1996, 88(3), 1122-1123.
120. Estey, E. H. Modulation of angiogenesis in patients with myelodysplastic syndrome. Best. Pract. Res. Clin. Haematol. 2004, 17(4), 623-639.
121. Aguayo, A.; Kantarjian, H.; Manshouri, T.; Gidel, C.; Estey, E.; Thomas, D.; Koller, C.; Estrov, Z.; O'Brien, S.; Keating, M.; Freireich, E.; Albitar, M. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000, 96(6), 2240-2245.
122. Zorat, F.; Shetty, V.; Dutt, D.; Lisak, L.; Nascimben, F.; Allampallam, K.; Dar, S.; York, A.; Gezer, S.; Venugopal, P.; Raza, A. The clinical and biological effects of thalidomide in patients with myelodysplastic syndromes. Br. J. Haematol. 2001, 115(4), 881-894.
123. Brunner, B.; Gunsilius, E.; Schumacher, P.; Zwierzina, H.; Gastl, G.; Stauder, R. Blood levels of angiogenin and vascular endothelial growth factor are elevated in myelodysplastic syndromes and in acute myeloid leukemia. J. Hematother. Stem Cell Res. 2002, 11(1), 119-125.
124. Wimazal, F.; Krauth, M. T.; Vales, A.; Bohm, A.; Agis, H.; Sonneck, K.; Aichberger, K. J.; Mayerhofer, M.; Simonitsch-Klupp, I.; Mullauer, L.; Sperr, W. R.; Valent, P. Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the bone marrow in patients with myelodysplastic syndromes: correlation between VEGF expression and the FAB category. Leuk. Lymphoma 2006, 47(3), 451-460.
125. Pruneri, G.; Bertolini, F.; Soligo, D.; Carboni, N.; Cortelezzi, A.; Ferrucci, P. F.; Buffa, R.; Lambertenghi-Deliliers, G.; Pezzella, F. Angiogenesis in myelodysplastic syndromes. Br. J. Cancer 1999, 81(8), 1398-1401.
126. Korkolopoulou, P.; Apostolidou, E.; Pavlopoulos, P. M.; Kavantzas, N.; Vyniou, N.; Thymara, I.; Terpos, E.; Patsouris, E.; Yataganas, X.; Davaris, P. Prognostic evaluation of the microvascular network in myelodysplastic syndromes. Leukemia 2001, 15(9), 1369-1376.
127. Epperson, D. E.; Nakamura, R.; Saunthararajah, Y.; Melenhorst, J.; Barrett, A. J. Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. Leuk. Res. 2001, 25(12), 1075-1083.
128. Smith, M. A.; Smith, J. G. The occurrence subtype and significance of haemopoietic inhibitory T cells (HIT cells) in myelodysplasia: an in vitro study. Leuk. Res. 1991, 15(7), 597-601.
129. Molldrem, J. J.; Caples, M.; Mavroudis, D.; Plante, M.; Young, N. S.; Barrett, A. J. Antithymocyte globulin for patients with myelodysplastic syndrome. Br. J. Haematol. 1997, 99(3), 699-705.
130. Jonasova, A.; Neuwirtova, R.; Cermak, J.; Vozobulova, V.; Mocikova, K.; Siskova, M.; Hochova, I. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br. J. Haematol. 1998, 100(2), 304-309.
131. Molldrem, J. J.; Jiang, Y. Z.; Stetler-Stevenson, M.; Mavroudis, D.; Hensel, N.; Barrett, A. J. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br. J. Haematol. 1998, 102(5), 1314-1322.
132. Melenhorst, J. J.; Eniafe, R.; Follmann, D.; Nakamura, R.; Kirby, M.; Barrett, A. J. Molecular and flow cytometric characterization of the CD4 and CD8 T-cell repertoire in patients with myelodysplastic syndrome. Br. J. Haematol. 2002, 119(1), 97-105.
133. Voulgarelis, M.; Giannouli, S.; Ritis, K.; Tzioufas, A. G. Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts. Eur. J. Clin. Invest. 2004, 34(10), 690-700.
134. Marisavljevic, D.; Kraguljac, N.; Rolovic, Z. Immunologic abnormalities in myelodysplastic syndromes: clinical features and characteristics of the lymphoid population. Med. Oncol. 2006, 23(3), 385-392.
135. Billstrom, R.; Johansson, H.; Johansson, B.; Mitelman, F. Immune-mediated complications in patients with myelodysplastic syndromes - clinical and cytogenetic features. Eur. J. Haematol. 1995, 55(1), 42-48.
136. Saitoh, K.; Miura, I.; Takahashi, N.; Miura, A. B. Fluorescence in situ hybridization of progenitor cells obtained by fluorescence-activated cell sorting for the detection of cells affected by chromosome abnormality trisomy 8 in patients with myelodysplastic syndromes. Blood 1998, 92(8), 2886-2892.
137. White, N. J.; Nacheva, E.; Asimakopoulos, F. A.; Bloxham, D.; Paul, B.; Green, A. R. Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B cells. Blood 1994, 83(10), 2809-2816.
138. Nilsson, L.; Astrand-Grundstrom, I.; Arvidsson, I.; Jacobsson, B.; Hellstrom-Lindberg, E.; Hast, R.; Jacobsen, S. E. Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level. Blood 2000, 96(6), 2012-2021.
139. Nilsson, L.; Astrand-Grundstrom, I.; Anderson, K.; Arvidsson, I.; Hokland, P.; Bryder, D.; Kjeldsen, L.; Johansson, B.; Hellstrom-Lindberg, E.; Hast, R.; Jacobsen, S. E. Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 2002, 100(1), 259-267.
140. Furukawa, Y. Cell cycle control during hematopoietic cell differentiation. Hum. Cell 1997, 10(3), 159-164.
141. Furukawa, Y.; Kikuchi, J.; Nakamura, M.; Iwase, S.; Yamada, H.; Matsuda, M. Lineage-specific regulation of cell cycle control gene expression during haematopoietic cell differentiation. Br. J. Haematol. 2000, 110(3), 663-673.
142. Shimizu, R.; Kuroha, T.; Ohneda, O.; Pan, X.; Ohneda, K.; Takahashi, S.; Philipsen, S.; Yamamoto, M. Leukemogenesis caused by incapacitated GATA-1 function. Mol. Cell Biol. 2004, 24(24), 10814-10825.
143. Dubart, A.; Romeo, P. H.; Vainchenker, W.; Dumenil, D. Constitutive expression of GATA-1 interferes with the cell-cycle regulation. Blood 1996, 87(9), 3711-3721.
144. Weiss, M. J.; Orkin, S. H. Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. Proc. Natl. Acad. Sci. USA 1995, 92(21), 9623-9627.
145. Briegel, K.; Lim, K. C.; Plank, C.; Beug, H.; Engel, J. D.; Zenke, M. Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. Genes Dev. 1993, 7(6), 1097-1109.
146. McDevitt, M. A.; Shivdasani, R. A.; Fujiwara, Y.; Yang, H.; Orkin, S. H. A "knockdown" mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. Proc. Natl. Acad. Sci. USA 1997, 94(13), 6781-6785.
147. Fadilah, S. A.; Cheong, S. K.; Roslan, H.; Rozie-Hanisa, M.; Yen, G. K. GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome. Leukemia 2002, 16(8), 1563-1565.
148. Cheson, B. D.; Greenberg, P. L.; Bennett, J. M.; Lowenberg, B.; Wijermans, P. W.; Nimer, S. D.; Pinto, A.; Beran, M.; de Witte, T. M.; Stone, R. M.; Mittelman, M.; Sanz, G. F.; Gore, S. D.; Schiffer, C. A.; Kantarjian, H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006, 108(2), 419-425.
149. Hellstrom-Lindberg, E. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br. J. Haematol. 1995, 89(1), 67-71.
150. Stein, R. S. The role of erythropoietin in the anemia of myelodysplastic syndrome. Clin. Lymphoma 2003, 4(Suppl. 1), S36-S40.
151. Hellstrom-Lindberg, E.; Negrin, R.; Stein, R.; Krantz, S.; Lindberg, G.; Vardiman, J.; Ost, A.; Greenberg, P. Erythroid response to treatment with GCSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br. J. Haematol. 1997, 99(2), 344-351.
152. Remacha, A. F.; Arrizabalaga, B.; Villegas, A.; Manteiga, R.; Calvo, T.; Julia, A.; Fernandez, F., I; Gonzalez, F. A.; Font, L.; Junca, J.; del Arco, A.; Malcorra, J. J.; Equiza, E. P.; de Mendiguren, B. P.; Romero, M. Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group. Haematologica 1999, 84(12), 1058-1064.
153. Negrin, R. S.; Stein, R.; Doherty, K.; Cornwell, J.; Vardiman, J.; Krantz, S.; Greenberg, P. L. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 1996, 87(10), 4076-4081.
154. Kasper, C.; Zahner, J.; Sayer, H. G. Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. J. Cancer Res. Clin. Oncol. 2002, 128(9), 497-502.
155. Terpos, E.; Mougiou, A.; Kouraklis, A.; Chatzivassili, A.; Michalis, E.; Giannakoulas, N.; Manioudaki, E.; Lazaridou, A.; Bakaloudi, V.; Protopappa, M.; Liapi, D.; Grouzi, E.; Parharidou, A.; Symeonidis, A.; Kokkini, G.; Laoutaris, N. P.; Vaipoulos, G.; Anagnostopoulos, N. I.; Christakis, J. I.; Meletis, J.; Bourantas, K. L.; Zoumbos, N. C.; Yataganas, X.; Viniou, N. A. Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br. J. Haematol. 2002, 118(1), 174-180.
156. Patton, J. F.; Sullivan, T.; Mun, Y.; Reeves, T.; Rossi, G.; Wallace, J. F. A retrospective cohort study to assess the impact of therapeutic substitution of darbepoetin alfa for epoetin alfa in anemic patients with myelodysplastic syndrome. J. Support. Oncol. 2005, 3(6), 419-426.
157. Mannone, L.; Gardin, C.; Quarre, M. C.; Bernard, J. F.; Vassilieff, D.; Ades, L.; Park, S.; Vaultier, S.; Hamza, F.; Beyne-rauzy, M. O.; Cheze, S.; Giraudier, S.; Agape, P.; Legros, L.; Voillat, L.; Dreyfus, F.; Fenaux, P. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br. J. Haematol. 2006, 133(5), 513-519.
158. Sierra, J.; Perez, W. S.; Rozman, C.; Carreras, E.; Klein, J. P.; Rizzo, J. D.; Davies, S. M.; Lazarus, H. M.; Bredeson, C. N.; Marks, D. I.; Canals, C.; Boogaerts, M. A.; Goldman, J.; Champlin, R. E.; Keating, A.; Weisdorf, D. J.; de Witte, T. M.; Horowitz, M. M. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood 2002, 100(6), 1997-2004.
159. Kuendgen, A.; Strupp, C.; Aivado, M.; Hildebrandt, B.; Haas, R.; Gattermann, N.; Germing, U. Myelodysplastic syndromes in patients younger than age 50. J. Clin. Oncol. 2006, 24(34), 5358-5365.
160. Cutler, C. S.; Lee, S. J.; Greenberg, P.; Deeg, H. J.; Perez, W. S.; Anasetti, C.; Bolwell, B. J.; Cairo, M. S.; Gale, R. P.; Klein, J. P.; Lazarus, H. M.; Liesveld, J. L.; McCarthy, P. L.; Milone, G. A.; Rizzo, J. D.; Schultz, K. R.; Trigg, M. E.; Keating, A.; Weisdorf, D. J.; Antin, J. H.; Horowitz, M. M. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 2004, 104(2), 579-585.
161. Martino, R.; Iacobelli, S.; Brand, R.; Jansen, T.; van Biezen, A.; Finke, J.; Bacigalupo, A.; Beelen, D.; Reiffers, J.; Devergie, A.; Alessandrino, E.; Mufti, G. J.; Barge, R.; Sierra, J.; Ruutu, T.; Boogaerts, M.; Falda, M.; Jouet, J. P.; Niederwieser, D.; De Witte, T. Retrospective comparison of reduced intensity conditioning and conventional high dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood 2006, 108(3), 836-846.
162. de Lima, M.; Anagnostopoulos, A.; Munsell, M.; Shahjahan, M.; Ueno, N.; Ippoliti, C.; Andersson, B. S.; Gajewski, J.; Couriel, D.; Cortes, J.; Donato, M.; Neumann, J.; Champlin, R.; Giralt, S. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004, 104(3), 865-872.
163. Scott, B. L.; Sandmaier, B. M.; Storer, B.; Maris, M. B.; Sorror, M. L.; Maloney, D. G.; Chauncey, T. R.; Storb, R.; Deeg, H. J. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 2006, 20(1), 128-135.
164. Shimoni, A.; Hardan, I.; Shem-Tov, N.; Yeshurun, M.; Yerushalmi, R.; Avigdor, A.; Ben Bassat, I.; Nagler, A. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 2006, 20(2), 322-328.
165. Alyea, E. P.; Kim, H. T.; Ho, V.; Cutler, C.; Deangelo, D. J.; Stone, R.; Ritz, J.; Antin, J. H.; Soiffer, R. J. Impact of Conditioning Regimen Intensity on Outcome of Allogeneic Hematopoietic Cell Transplantation for Advanced Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Biol. Blood Marrow Transplant. 2006, 12(10), 1047-1055.
166. Mattijssen, V.; Schattenberg, A.; Schaap, N.; Preijers, F.; De Witte, T. Outcome of allogeneic bone marrow transplantation with lymphocyte-depleted marrow grafts in adult patients with myelodysplastic syndromes. Bone Marrow Transplant. 1997, 19(8), 791-794.
167. Ooi, J. The efficacy of unrelated cord blood transplantation for adult myelodysplastic syndrome. Leuk. Lymphoma 2006, 47(4), 599-602.
168. Lu, D. P.; Dong, L.; Wu, T.; Huang, X. J.; Zhang, M. J.; Han, W.; Chen, H.; Liu, D. H.; Gao, Z. Y.; Chen, Y. H.; Xu, L. P.; Zhang, Y. C.; Ren, H. Y.; Li, D.; Liu, K. Y. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 2006, 107(8), 3065-3073.
169. Kizaki, M.; Koeffler, H. P. Differentiation-inducing agents in the treatment of myelodysplastic syndromes. Semin. Oncol. 1992, 19(1), 95-105.
170. Silverman, L. R.; Demakos, E. P.; Peterson, B. L.; Kornblith, A. B.; Holland, J. C.; Odchimar-Reissig, R.; Stone, R. M.; Nelson, D.; Powell, B. L.; DeCastro, C. M.; Ellerton, J.; Larson, R. A.; Schiffer, C. A.; Holland, J. F. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J. Clin. Oncol. 2002, 20(10), 2429-2440.
171. Silverman, L. R.; McKenzie, D. R.; Peterson, B. L.; Holland, J. F.; Backstrom, J. T.; Beach, C. L.; Larson, R. A. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J. Clin. Oncol. 2006, 24(24), 3895-3903.
172. Zagonel, V.; Lo, R. G.; Marotta, G.; Babare, R.; Sardeo, G.; Gattei, V.; De, A. V.; Monfardini, S.; Pinto, A. 5-Aza-2′-deoxycytidine (Decitabine) induces trilineage response in unfavourable myelodysplastic syndromes. Leukemia 1993, 7(Suppl. 1), 30-35.
173. Wijermans, P. W.; Krulder, J. W.; Huijgens, P. C.; Neve, P. Continuous infusion of low-dose 5-Aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia 1997, 11(Suppl. 1), S19-S23.
174. Kantarjian, H.; Issa, J. P.; Rosenfeld, C. S.; Bennett, J. M.; Albitar, M.; DiPersio, J.; Klimek, V.; Slack, J.; de Castro, C.; Ravandi, F.; Helmer, R., III; Shen, L.; Nimer, S. D.; Leavitt, R.; Raza, A.; Saba, H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006, 106(8), 1794-1803.
175. Kantarjian, H.; Oki, Y.; Garcia-Manero, G.; Huang, X.; O'Brien, S.; Cortes, J.; Faderl, S.; Bueso-Ramos, C.; Ravandi, F.; Estrov, Z.; Ferrajoli, A.; Wierda, W.; Shan, J.; Davis, J.; Giles, F.; Saba, H. I.; Issa, J. P. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007, 109(1), 52-57.
176. Schreiber, S. L.; Bernstein, B. E. Signaling network model of chromatin. Cell 2002, 111(6), 771-778.
177. Dokmanovic, M.; Marks, P. A. Prospects: histone deacetylase inhibitors. J. Cell Biochem. 2005, 96(2), 293-304.
178. Kuendgen, A.; Strupp, C.; Aivado, M.; Bernhardt, A.; Hildebrandt, B.; Haas, R.; Germing, U.; Gattermann, N. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 2004, 104(5), 1266-1269.
179. Kuendgen, A.; Knipp, S.; Fox, F.; Strupp, C.; Hildebrandt, B.; Steidl, C.; Germing, U.; Haas, R.; Gattermann, N. Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann. Hematol. 2005, 84(Suppl. 13), 61-66.
180. Saunthararajah, Y.; Nakamura, R.; Nam, J. M.; Robyn, J.; Loberiza, F.; Maciejewski, J. P.; Simonis, T.; Molldrem, J.; Young, N. S.; Barrett, A. J. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 2002, 100(5), 1570-1574.
181. Candoni, A.; Silvestri, F.; Buonamici, S.; Li, D.; Reddy, P.; Galili, N.; Nucifora, G.; Raza, A. Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin. Hematol. 2004, 41(2 Suppl. 4), 13-20.
182. Galili, N.; Raza, A. Immunomodulatory drugs in myelodysplastic syndromes. Expert Opin. Investig. Drugs 2006, 15(7), 805-813.
183. Tamilarasan, K. P.; Kolluru, G. K.; Rajaram, M.; Indhumathy, M.; Saranya, R.; Chatterjee, S. Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration of endothelial cells. BMC Cell Biol. 2006, 7, 17-29.
184. Geitz, H.; Handt, S.; Zwingenberger, K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996, 31(2-3), 213-221.
185. D'Amato, R. J.; Loughnan, M. S.; Flynn, E.; Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. USA 1994, 91(9), 4082-4085.
186. Mitsiades, N.; Mitsiades, C. S.; Poulaki, V.; Chauhan, D.; Richardson, P. G.; Hideshima, T.; Munshi, N. C.; Treon, S. P.; Anderson, K. C. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002, 99(12), 4525-4530.
187. Mitsuyasu, R. T.; Champlin, R. E.; Gale, R. P.; Ho, W. G.; Lenarsky, C.; Winston, D.; Selch, M.; Elashoff, R.; Giorgi, J. V.; Wells, J. Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial. Ann. Intern. Med. 1986, 105(1), 20-26.
188. Raza, A.; Meyer, P.; Dutt, D.; Zorat, F.; Lisak, L.; Nascimben, F.; du, R. M.; Kaspar, C.; Goldberg, C.; Loew, J.; Dar, S.; Gezer, S.; Venugopal, P.; Zeldis, J. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood 2001, 98(4), 958-965.
189. Strupp, C.; Germing, U.; Aivado, M.; Misgeld, E.; Haas, R.; Gattermann, N. Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia 2002, 16(1), 1-6.
190. Musto, P.; Falcone, A.; Sanpaolo, G.; Bisceglia, M.; Matera, R.; Carella, A. M. Thalidomide abolishes transfusion-dependence in selected patients with myelodysplastic syndromes. Haematologica 2002, 87(8), 884-886.
191. Bowen, D.; MacIlwaine, L.; Cavanagh, J.; Killick, S.; Culligan, D.; Thomson, E.; Mufti, G. Thalidomide therapy for low-risk Myelodysplasia. Leuk. Res. 2005, 29(2), 235-236.
192. Bouscary, D.; Legros, L.; Tulliez, M.; Dubois, S.; Mahe, B.; Beyne-Rauzy, O.; Quarre, M. C.; Vassilief, D.; Varet, B.; Aouba, A.; Gardembas, M.; Giraudier, S.; Guerci, A.; Rousselot, P.; Gaillard, F.; Moreau, A.; Rousselet, M. C.; Ifrah, N.; Fenaux, P.; Dreyfus, F. A non-randomised dose-escalating phase II study of thalidomide for the treatment of patients with low-risk myelodysplastic syndromes: the Thal-SMD-2000 trial of the Groupe Francais des Myelodysplasies. Br. J. Haematol. 2005, 131(5), 609-618.
193. Corral, L. G.; Haslett, P. A.; Muller, G. W.; Chen, R.; Wong, L. M.; Ocampo, C. J.; Patterson, R. T.; Stirling, D. I.; Kaplan, G. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J. Immunol. 1999, 163(1), 380-386.
194. Davies, F. E.; Raje, N.; Hideshima, T.; Lentzsch, S.; Young, G.; Tai, Y. T.; Lin, B.; Podar, K.; Gupta, D.; Chauhan, D.; Treon, S. P.; Richardson, P. G.; Schlossman, R. L.; Morgan, G. J.; Muller, G. W.; Stirling, D. I.; Anderson, K. C. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001, 98(1), 210-216.
195. Maier, S. K.; Hammond, J. M. Role of lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome. Ann. Pharmacother. 2006, 40(2), 286-289.
196. List, A.; Kurtin, S.; Roe, D. J.; Buresh, A.; Mahadevan, D.; Fuchs, D.; Rimsza, L.; Heaton, R.; Knight, R.; Zeldis, J. B. Efficacy of lenalidomide in myelodysplastic syndromes. N. Engl. J. Med. 2005, 352(6), 549-557.
197. Sekeres, M. A.; List, A. Immunomodulation in myelodysplastic syndromes. Best. Pract. Res. Clin. Haematol. 2006, 19(4), 757-767.
198. Hellstrom-Lindberg, E.; Ahlgren, T.; Beguin, Y.; Carlsson, M.; Carneskog, J.; Dahl, I. M.; Dybedal, I.; Grimfors, G.; Kanter-Lewensohn, L.; Linder, O.; Luthman, M.; Lofvenberg, E.; Nilsson-Ehle, H.; Samuelsson, J.; Tangen, J. M.; Winqvist, I.; Oberg, G.; Osterborg, A.; Ost, A. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 1998, 92(1), 68-75.
199. Meletis, J.; Viniou, N.; Terpos, E. Novel agents for the management of myelodysplastic syndromes. Med. Sci. Monit. 2006, 12(9), RA194-RA206.
200. Gore, S. D.; Baylin, S.; Sugar, E.; Carraway, H.; Miller, C. B.; Carducci, M.; Grever, M.; Galm, O.; Dauses, T.; Karp, J. E.; Rudek, M. A.; Zhao, M.; Smith, B. D.; Manning, J.; Jiemjit, A.; Dover, G.; Mays, A.; Zwiebel, J.; Murgo, A.; Weng, L. J.; Herman, J. G. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 2006, 66(12), 6361-6369.
201. Maslak, P.; Chanel, S.; Camacho, L. H.; Soignet, S.; Pandolfi, P. P.; Guernah, I.; Warrell, R.; Nimer, S. Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacitidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia 2006, 20(2), 212-217.
202. Oka, Y.; Tsuboi, A.; Taguchi, T.; Osaki, T.; Kyo, T.; Nakajima, H.; Elisseeva, O. A.; Oji, Y.; Kawakami, M.; Ikegame, K.; Hosen, N.; Yoshihara, S.; Wu, F.; Fujiki, F.; Murakami, M.; Masuda, T.; Nishida, S.; Shirakata, T.; Nakatsuka, S.; Sasaki, A.; Udaka, K.; Dohy, H.; Aozasa, K.; Noguchi, S.; Kawase, I.; Sugiyama, H. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc. Natl. Acad. Sci. USA 2004, 101(38), 13885-13890.
203. Tallman, M. S.; Andersen, J. W.; Schiffer, C. A.; Appelbaum, F. R.; Feusner, J. H.; Ogden, A.; Shepherd, L.; Willman, C.; Bloomfield, C. D.; Rowe, J. M.; Wiernik, P. H. All-trans-retinoic acid in acute promyelocytic leukemia. N. Engl. J. Med. 1997, 337(15), 1021-1028.
204. Santini, V.; Ferrini, P. R. Differentiation therapy of myelodysplastic syndromes: fact or fiction? Br. J. Haematol. 1998, 102(5), 1124-1138.
205. Nand, S.; Ellis, T.; Messmore, H.; Fisher, S. G.; Gaynor, E.; Fisher, R. I. Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. Leukemia 1992, 6(3), 220-223.
206. Maerevoet, M.; Van Den, N. E.; Delannoy, A.; Ferrant, A.; Martiat, P.; Bosly, A.; Fauchet, M.; Michaux, J. L. Limited activity of mini-dose interferon alpha-2a in the treatment of myelodysplastic syndrome. Leuk. Lymphoma 1996, 21(5-6), 519-520.
207. Holcombe, R. F. Mini-dose interferon alpha-2a in the treatment of myelodysplasia. Leukemia 1993, 7(2), 192-195.
208. Elias, L.; Hoffman, R.; Boswell, S.; Tensen, L.; Bonnem, E. M. A trial of recombinant alpha 2 interferon in the myelodysplastic syndromes: I. Clinical results. Leukemia 1987, 1(2), 105-110.
209. Gisslinger, H.; Chott, A.; Linkesch, W.; Fritz, E.; Ludwig, H. Long-term alpha-interferon therapy in myelodysplastic syndromes. Leukemia 1990, 4(2), 91-94.
210. Motomura, S.; Kanamori, H.; Maruta, A.; Kodama, F.; Ohkubo, T. The effect of 1-hydroxyvitamin D3 for prolongation of leukemic transformation-free survival in myelodysplastic syndromes. Am. J. Hematol. 1991, 38(1), 67-68.
211. Koeffler, H. P.; Aslanian, N.; O'Kelly, J. Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome. Leuk. Res. 2005, 29(11), 1259-1262.
212. Mellibovsky, L.; Diez, A.; Perez-Vila, E.; Serrano, S.; Nacher, M.; Aubia, J.; Supervia, A.; Recker, R. R. Vitamin D treatment in myelodysplastic syndromes. Br. J. Haematol. 1998, 100(3), 516-520.
213. Ganser, A.; Seipelt, G.; Verbeek, W.; Ottmann, O. G.; Maurer, A.; Kolbe, K.; Hess, U.; Elsner, S.; Reutzel, R.; Wormann, B. Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes. Leukemia 1994, 8(3), 369-375.
214. Hofmann, W. K.; Ganser, A.; Seipelt, G.; Ottmann, O. G.; Zander, C.; Geissler, G.; Hoffmann, K.; Hoffken, K.; Fischer, J. T.; Isele, G.; Hoelzer, D. Treatment of patients with low-risk myelodysplastic syndromes using a combination of all-trans retinoic acid, interferon alpha, and granulocyte colony-stimulating factor. Ann. Hematol. 1999, 78(3), 125-130.
215. Matsui, W. H.; Gladstone, D. E.; Vala, M. S.; Barber, J. P.; Brodsky, R. A.; Smith, B. D.; Jones, R. J. The role of growth factors in the activity of pharmacological differentiation agents. Cell Growth Differ. 2002, 13(6), 275-283.
216. Matsui, W.; Huff, C. A.; Vala, M.; Barber, J.; Smith, B. D.; Jones, R. J. Antitumour activity of interferon-alpha in multiple myeloma: role of interleukin 6 and tumor cell differentiation. Br. J. Haematol. 2003, 121(2), 251-258.
217. Matsui, W.; Smith, B. D.; Vala, M.; Beal, N.; Huff, C. A.; Diehl, L. F.; Jones, R. J. Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia. Br. J. Haematol. 2005, 128(6), 853-862.
218. Williams, C. D.; Linch, D. C.; Watts, M. J.; Thomas, N. S. Characterization of cell cycle status and E2F complexes in mobilized CD34+ cells before and after cytokine stimulation. Blood 1997, 90(1), 194-203.
219. Williams, G. T.; Smith, C. A.; Spooncer, E.; Dexter, T. M.; Taylor, D. R. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 1990, 343(6253), 76-79.