Novel epigenetic targets in lymphoproliferative disorders

Current Cancer Drug Targets

Volumn 8, Issue 5, 2008, Pages 378-391

  Delgado, Julio ^a  

^a HOSPITAL DE LA SANTA CREU I SANT PAU   (Spain)

Author keywords

Chronic lymphocytic leukemia; Demethylating agents; DNA methylation; Histone acetylation; Histone deacetylase inhibitors; Hodgkin's lymphoma; Non Hodgkin's lymphoma

Indexed keywords

3 PHENYLSULFAMOYLCINNAMOHYDROXAMIC ACID; 5 AZA 2' DEOXYCYTIDINE; AMINOBENZOIC ACID DERIVATIVE; ARYLBUTYRIC ACID DERIVATIVE; AZACITIDINE; BELINOSTAT; CYTOKINE RECEPTOR ANTAGONIST; DENILEUKIN DIFTITOX; DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE INHIBITOR; HISTONE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR BLOCKING AGENT; MG 98; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; OLIGONUCLEOTIDE; PANOBINOSTAT; PROCAINAMIDE; PSAMMAPLIN; RETINOID; RG 108; ROMIDEPSIN; TRICHOSTATIN A; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; ZEBULARINE;

ACETYLATION; ANEMIA; ANOREXIA; B CELL LYMPHOMA; B LYMPHOCYTE; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; BONE MARROW TUMOR; CANCER CELL; CANCER CELL CULTURE; CANCER CLASSIFICATION; CARCINOGENESIS; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DEHYDRATION; DIARRHEA; DNA METHYLATION; DRUG TARGETING; EPIGENETICS; FATIGUE; FOLLICULAR LYMPHOMA; GENE MUTATION; GENE SILENCING; HODGKIN DISEASE; HUMAN; LARGE CELL LYMPHOMA; LOW DRUG DOSE; LYMPHATIC LEUKEMIA; LYMPHATIC SYSTEM TUMOR; LYMPHOID CELL; LYMPHOPROLIFERATIVE DISEASE; MANTLE CELL LYMPHOMA; MONOTHERAPY; NAUSEA; NONHODGKIN LYMPHOMA; NONHUMAN; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN MODIFICATION; REVIEW; SMALL LYMPHOCYTIC LEUKEMIA; T CELL LYMPHOMA; T LYMPHOCYTE; THROMBOCYTOPENIA; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE; UNSPECIFIED SIDE EFFECT; VOMITING;

EPIGENESIS, GENETIC; GENE SILENCING; HUMANS; LYMPHOPROLIFERATIVE DISORDERS; PROMOTER REGIONS (GENETICS);

EID: 48849091231     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800908785133222     Document Type: Review

References (138)

1. Das, P. M.; Singal, R. DNA methylation and cancer. J. Clin. Oncol. 2004, 22, 4632-4642.
2. Smith, L. T.; Otterson, G. A.; Plass, C. Unraveling the epigenetic code of cancer for therapy. Trends Genet. 2007, 23, 449-456.
3. Amir, R. E.; Van den Veyver, I. B.; Wan, M.; Tran, C. Q.; Francke, U.; Zoghbi, H. Y. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 1999, 23, 185-188.
4. Richardson, B.; Scheinbart, L.; Strahler, J.; Gross, L.; Hanash, S.; Johnson, M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1990, 33, 1665-1673.
5. Post, W. S.; Goldschmidt-Clermont, P. J.; Wilhide, C. C.; Heldman, A. W.; Sussman, M. S.; Ouyang, P.; Milliken, E. E.; Issa, J. P. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc. Res. 1999, 43, 985-991.
6. Paz, M. F.; Avila, S.; Fraga, M. F.; Pollan, M.; Capella, G.; Peinado, M. A.; Sanchez-Cespedes, M.; Herman, J. G.; Esteller, M. Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors. Cancer Res. 2002, 62, 4519-4524.
7. Bird, A. P. CpG-rich islands and the function of DNA methylation. Nature 1986, 321, 209-213.
8. Jones, P. L.; Veenstra, G. J.; Wade, P. A.; Vermaak, D.; Kass, S. U.; Landsberger, N.; Strouboulis, J.; Wolffe, A. P. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat. Genet. 1998, 19, 187-191.
9. Santini, V.; Kantarjian, H. M.; Issa, J. P. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann. Intern. Med. 2001, 134, 573-586.
10. Berger, S. L. The complex language of chromatin regulation during transcription. Nature 2007, 447, 407-412.
11. Glaser, K. B. HDAC inhibitors: clinical update and mechanism-based potential. Biochem. Pharmacol. 2007, 74, 659-671.
12. Minucci, S.; Maccarana, M.; Cioce, M.; De Luca, P.; Gelmetti, V.; Segalla, S.; Di Croce, L.; Giavara, S.; Matteucci, C.; Gobbi, A.; Bianchini, A.; Colombo, E.; Schiavoni, I.; Badaracco, G.; Hu, X.; Lazar, M. A.; Landsberger, N.; Nervi, C.; Pelicci, P. G. Oligomerization of RAR and AML1 transcription factors as a novel mechanism of oncogenic activation. Mol. Cell. 2000, 5, 811-820.
13. Conley, B. A.; Wright, J. J.; Kummar, S. Targeting epigenetic abnormalities with histone deacetylase inhibitors. Cancer 2006, 107, 832-840.
14. Cameron, E. E.; Bachman, K. E.; Myohanen, S.; Herman, J. G.; Baylin, S. B. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 1999, 21, 103-107.
15. de Bustros, A.; Nelkin, B. D.; Silverman, A.; Ehrlich, G.; Poiesz, B.; Baylin, S. B. The short arm of chromosome 11 is a 'hot spot' for hypermethylation in human neoplasia. Proc. Natl. Acad. Sci. USA 1988, 85, 5693-5697.
16. Herman, J. G.; Latif, F.; Weng, Y.; Lerman, M. I.; Zbar, B.; Liu, S.; Samid, D.; Duan, D. S. R.; Gnarra, J. R.; Linehan, W. M.; Baylin, S. B. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA 1994, 91, 9700-9704.
17. Esteller, M.; Corn, P. G.; Baylin, S. B.; Herman, J. G. A gene hypermethylation profile of human cancer. Cancer Res. 2001, 61, 3225-3229.
18. Paz, M. F.; Fraga, M. F.; Avila, S.; Guo, M.; Pollan, M.; Herman, J. G.; Esteller, M. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res. 2003, 63, 1114-1121.
19. Esteller, M. Cancer epigenomics: DNA methylomes and histone modification maps. Nat. Rev. Genet. 2007, 8, 286-298.
20. 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, 837-841.
21. Baur, A. S.; Shaw, P.; Burri, N.; Delacretaz, F.; Bosman, F. T.; Chaubert, P. Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas. Blood 1999, 94, 1773-1781.
22. Pinyol, M.; Hernandez, L.; Cazorla, M.; Balbin, M.; Jares, P.; Fernandez, P. L.; Montserrat, E.; Cardesa, A.; Lopez-Otin, C.; Campo, E. Deletions and loss of expression of p16INK4a and p21Waf1 genes are associated with aggressive variants of mantle cell lymphomas. Blood 1997, 89, 272-280.
23. Garcia, M. J.; Martinez-Delgado, B.; Cebrian, A.; Martinez, A.; Benitez, J.; Rivas, C. Different incidence and pattern of p15INK4b and p16INK4a promoter region hypermethylation in Hodgkin's and CD30-positive non-Hodgkin's lymphomas. Am. J. Pathol. 2002, 161, 1007-1013.
24. Navas, I. C.; Ortiz-Romero, P. L.; Villuendas, R.; Martinez, P.; Garcia, C.; Gomez, E.; Rodriguez, J. L.; Garcia, D.; Vanaclocha, F.; Iglesias, L.; Piris, M. A.; Algara, P. p16(INK4a) gene alterations are frequent in lesions of mycosis fungoides. Am. J. Pathol. 2000, 156, 1565-1572.
25. Nosaka, K.; Maeda, M.; Tamiya, S.; Sakai, T.; Mitsuya, H.; Matsuoka, M. Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia. Cancer Res. 2000, 60, 1043-1048.
26. Gonzalez-Paz, N.; Chng, W. J.; McClure, R. F.; Blood, E.; Oken, M. M.; Van Ness, B.; James, C. D.; Kurtin, P. J.; Henderson, K.; Hamann, G. J.; Gertz, M.; Lacy, M.; Dispenzieri, A.; Greipp, P. R.; Fonseca, R. Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications. Blood 2007, 109, 1228-1232.
27. van Doorn, R.; Zoutman, W. H.; Dijkman, R.; de Menezes, R. X.; Commandeur, S.; Mulder, A. A.; van der Velden, P. A.; Vermeer, M. H., Willemze, R.; Yan, P. S.; Huang, T. H.; Tensen, C. P. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J. Clin. Oncol. 2007, 23, 3886-3896.
28. Rossi, D.; Capello, D.; Gloghini, A.; Franceschetti, S.; Paulli, M.; Bhatia, K.; Saglio, G.; Vitolo, U.; Pileri, S. A.; Esteller, M.; Carbone, A.; Gaidano, G. Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia. Haematologica 2004, 89, 154-164.
29. Li, Y.; Nagai, H.; Ohno, T.; Yuge, M.; Hatano, S.; Ito, E.; Mori, N.; Saito, H.; Kinoshita, T. Aberrat DNA methylation of p57(KIP2) gene in the promoter region in lymphoid malignancies of B-cell phenotype. Blood 2002, 100, 2572-2577.
30. 6-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. J. Natl. Cancer Inst. 2002, 94, 26-32.
31. Ying, J.; Srivastava, G.; Gao, Z.; Zhang, X.; Murray, P.; Ambinder, R.; Tao, Q. Promoter hypermethylation of the cyclin-dependent kinase inhibitor (CDKI) gene p21WAF1/CIP1/SDI1 is rare in various lymphomas and carcinomas. Blood 2004, 103, 743-746.
32. Rowley, J. D.; Reshmi, S.; Sobulo, O.; Musvee, T.; Anastasi, J.; Raimondi, S.; Schneider, N. R.; Barredo, J. C.; Cantu, E. S.; Schlegelberger, B.; Behm, F.; Doggett, N. A.; Borrow, J.; Zeleznik-Le, N. All patients with the t(11;16) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997, 90, 535-541.
33. Garcia-Manero, G.; Yang, H.; Bueso-Ramos, C.; Ferrajoli, A.; Cortes, J.; Wierda, W. G.; Faderl, S.; Koller, C.; Morris, G.; Rosner, G.; Loboda, A.; Fantin, V. R.; Randolph, S. S.; Hardwick, J. S.; Reilly, J. F.; Chen, C.; Ricker, J. L.; Secrist, J. P.; Richon, V. M.; Frankel, S. R.; Kantarjian, H. M. Phase I study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced leukemias and myelodysplastic syndromes. Blood 2008, 111, 1060-1066.
34. Bereshchenko, O. R.; Gu, W.; Dalla-Favera, R. Acetylation inactivates de transcriptional repressor BCL6. Nat. Genet. 2002, 32, 606-613.
35. O'Connor, O. A.; Heaney, M. L.; Schwartz, L.; Richardson, S.; Willim, R.; MacGregor-Cortelli, B.; Curly, T.; Moskowitz, C.; Portlock, C.; Horwitz, S.; Zelenetz, A. D.; Frankel, S.; Richon, V.; Marks, P.; Kelly, W. K. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J. Clin. Oncol. 2006, 24, 166-173.
36. Issa, J. P. Aging, DNA methylation and cancer. Crit. Rev. Oncol. Hematol. 1999, 32, 31-43.
37. Toyota, M.; Ahuja, N.; Ohe-Toyota, M.; Herman, J. G.; Baylin, S. B.; Issa, J. P. J. CpG island methylator phenotype in colorectal cancer. Proc. Natl. Acad. Sci. USA 1999, 96, 8681-8686.
38. Schlesinger, Y.; Straussman, R.; Keshet, I.; Farkash, S.; Hecht, M.; Zimmerman, J.; Eden, E.; Yakhini, Z.; Ben-Shushan, E.; Reubinoff, B. E.; Bergman, Y.; Simon, I.; Cedar, H. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet. 2007, 39, 232-236.
39. Widschwendter, M.; Fiegl, H.; Egle, D.; Mueller-Holzner, E.; Spizzo, G.; Marth, C.; Weisenberger, D. J.; Campan, M.; Young, J.; Jacobs, I.; Laird, P. W. Epigenetic stem cell signature in cancer. Nat. Genet. 2007, 39, 157-158.
40. Jaffe, E. S.; Harris, N. L.; Stein, H.; Vardiman, J. W., eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues; IARC Press: Lyon, France, 2001.
41. Hayslip, J.; Montero, A. Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review. Mol. Cancer 2006, 5, 44.
42. Taylor, K. H.; Kramer, R. S.; Davis, J. W.; Guo, J.; Duff, D. J.; Xu, D.; Caldwell, C. W.; Shi, H. Ultradeep bisulfite sequencing analysis of DNA methylation patterns in multiple gene promoters by 454 sequencing. Cancer Res. 2007, 67, 8511-8518.
43. Li, Y. Q.; Zhou, P. Z.; Zheng, X. D.; Walsh, C. P.; Xu, G. L. Association of DNMT3 and thymine DNA glycosylase links DNA methylation with base-excision repair. Nucleic Acids Res. 2007, 35, 390-400.
44. Martin-Subero, J. I.; Ballestar, E.; Esteller, M.; Siebert, R. Towards defining the lymphoma methylome. Leukemia 2006, 20, 1658-1660.
45. Ellis, T. M.; Moser, T. M.; Le, P. T.; Flanigan, R. C.; Kwon, E. D. Alterations in peripheral B-cells and B-cell progenitors following androgen ablation in mice. Int. Immunol. 2001, 13, 553-558.
46. Yang, H; Chen, C. M.; Yan, P; Huang, T. H.; Shi, H.; Burger, M.; Nimmrich, I.; Maier, S.; Berlin, K.; Caldwell, C. W. The androgen receptor gene is preferentially hypermethylated in follicular non-Hodgkin's lymphomas. Clin. Cancer Res. 2003, 9, 4034-4042.
47. Koyama, M.; Oka, T.; Ouchida, M.; Nakatani, Y.; Nishiuchi, R.; Yoshino, T.; Hayashi, K.; Akagi, T.; Seino, Y. Activated proliferation of B-cell lymphomas/leukemias with the SHP1 gene silencing by aberrant CpG methylation. Lab. Invest. 2003, 83, 1849-1858.
48. Kay, N. E.; O'Brien, S. M.; Pettitt, A. R.; Stilgenbauer, S. The role of prognostic factors in assessing 'high-risk' subgroups of patients with chronic lymphocytic leukemia. Leukemia 2007, 21, 1885-1891.
49. Hamblin, T. J.; Davis, Z.; Gardiner, A.; Oscier, D. G.; Stevenson, F. K. Unmutated IgVH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999, 94, 1848-1854.
50. Dohner, H.; Stilgenbauer, S.; Benner, A.; Leupoldt, E.; Krober, A.; Bullinger, L.; Dohner, K.; Bentz, M.; Lichter, P. Genomic aberrations and survival in chronic lymphocytic leukemia. N. Engl. J. Med. 2000, 343, 1910-1916.
51. Raval, A.; Byrd, J. C.; Plass, C. Epigenetics in chronic lymphocytic leukemia. Semin. Oncol. 2006, 33, 157-166.
52. Wahlfors, J.; Hiltunen, H.; Heinonen, K.; Hamalainen, E.; Alhonen, L.; Janne, J. Genomic hypomethylation in human chronic lymphocytic leukemia. Blood 1992, 80, 2074-2080.
53. Hanada, M.; Delia, D.; Aiello, A.; Stadtmauer, E.; Reed, J. C. Bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993, 82, 1820-1828.
54. Kantharidis, P.; El-Osta, A.; deSilva, M.; Wall, D. M. P.; Hu, X. F.; Slater, A.; Nadalin, G.; Parkin, J. D.; Zalcberg, J. R. Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance. Clin. Cancer Res. 1997, 3, 2025-2032.
55. Yuille, M. R.; Condie, A.; Stone, E. M.; Wilsher, J.; Bradshaw, P. S.; Brooks, L.; Catovsky, D. TCL1 is activated by chromosomal rearrangement or by hypomethylation. Genes Chromosomes Cancer 2001, 30, 336-341.
56. Bichi, R.; Shinton, S. A.; Martin, E. S.; Koval, A.; Calin, G. A.; Cesari, R.; Russo, G.; Hardy, R. R. Croce, C. M. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc. Natl. Acad. Sci. USA 2002, 99, 6955-6960.
57. Rush, L. J.; Raval, A.; Funchain, P.; Johnson, A. J.; Smith, L.; Lucas, D. M.; Bembea, M.; Liu, T. H. Heerema, N. A.; Rassenti, L.; Liyanarachchi, S.; Davuluri, R.; Byrd, J. C.; Plass, C. Epigenetic profiling in chronic lymphocytic leukemia reveals novel methylation targets. Cancer Res. 2004, 64, 2424-2433.
58. Guo, J.; Burger, M.; Nimmrich, I.; Maier, S.; Becker, E.; Genc, B.; Duff, D.; Rahmatpanah, F.; Chitma-Matsiga, R.; Shi, H.; Berlin, K.; Huang, T. H. M.; Caldwell, C. W. Differential DNA methylation of gene promoters in small B-cell lymphomas. Am. J. Clin. Pathol. 2005, 124, 430-439.
59. Maestro, R.; Dei Tos, A. P.; Hamamori, Y.; Krasnokutsky, S.; Sartorelli, V.; Kedes, L.; Doglioni, C.; Beach, D. H.; Hannon, G. J. Twist is a potential oncogene that inhibits apoptosis. Genes Dev. 1999, 13, 2207-2217.
60. Raval, A.; Lucas, D. M.; Matkovic, J. J.; Bennett, K. L.; Liyanarachchi, S.; Young, D. C.; Rassenti, L.; Kipps, T. J.; Grever, M. R.; Byrd, J. C.; Plass, C. TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia. J. Clin. Oncol. 2005, 23, 3877-3885.
61. Rosenwald, A.; Alizadeh, A. A.; Widhopf, G.; Simon, R.; Davis, R. E.; Yu, X.; Yang, L.; Pickeral, O. K.; Rassenti, L. Z.; Powell, J.; Botstein, D.; Byrd, J. C.; Grever, M. R.; Cheson, B. D.; Chiorazzi, N.; Wilson, W. H.; Kipps, T. J.; Brown, P. O.; Staudt, L. M. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J. Exp. Med. 2001, 194, 1639-1647.
62. Dann, C. E.; Hsieh, J. C.; Rattner, A.; Sharma, D.; Nathans, J; Leahy, D. J. Insights into Wnt binding and signalling from the structures of two frizzled cysteine-rich domains. Nature 2001, 412, 86-90.
63. Liu, T. H.; Raval, A.; Chen, S. S.; Matkovic, J. J.; Byrd, J. C.; Plass, C. CpG island methylation and expression of the secreted frizzled-related protein gene family in chronic lymphocytic leukemia. Cancer Res. 2006, 66, 653-658.
64. Ostman, A.; Hellberg, C.; Böhmer, F. D. Protein-tyrosine phosphatases and cancer. Nat. Rev. Cancer 2006, 6, 307-320.
65. Motiwala, T.; Majumder, S.; Kutay, H.; Smith, D. S.; Neuberg, D. S.; Lucas, D. M.; Byrd, J. C.; Grever, M.; Jacob, S. T. Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia. Clin. Cancer Res. 2007, 13, 3174-3181.
66. Raval, A.; Tanner, S. M.; Byrd, J. C.; Angerman, E. B.; Perko, J. D.; Chen, S. S.; Hackanson, B.; Grever, M. R.; Lucas, D. M.; Matkovic, J. J.; Lin, T. S.; Kipps, T. J.; Murray, F.; Weisenburger, D.; Sanger, W.; Lynch, J.; Watson, P.; Jansen, M.; Yoshinaga, Y.; Rosenquist, R.; de Jong, P. J.; Coggill, P.; Beck, S.; Lynch, H.; de la Chapelle, A.; Plass, C. Downregulation of Death-Associated Protein Kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 2007, 129, 879-890.
67. Brenner, R.; Deplus, C.; Didelot, A.; Loriot, E.; Vire, C.; De Smet, A.; Gutierrez, D.; Danovi, D.; Bernard, D.; Boon, T.; Pelicci, P. G.; Amati, B.; Kouzarides, T.; de Launoit, Y.; Di Croce, L.; Fuks, F. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J. 2005, 24, 336-346.
68. Alizadeh, A. A.; Eisen, M. B.; Davis, R. E.; Ma, C.; Lossos, I. S.; Rosenwald, A.; Boldrick, J. C.; Sabet, H.; Tran, T.; Yu, X.; Powell, J. I.; Yang, L.; Marti, G. E.; Moore, T.; Hudson Jr, J.; Lu, L.; Lewis, D. B.; Tibshirani, R.; Sherlock, G.; Chan, W. C.; Greiner, T. C.; Weisenburger, D. D.; Armitage, J. O.; Warnke, R.; Levy, R.; Wilson, W.; Grever, M. R.; Byrd, J. C.; Botstein, D.; Brown, P. O.; Staudt, L. M. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403, 503-511.
69. Cattoretti, G.; Pasqualucci, L.; Ballon, G.; Tam, W.; Nandula, S. V.; Shen, Q.; Mo, T.; Murty, V. V.; Dalla-Favera, R. De-regulated BCL6 expression recapitulates the pathogenesis of human diffuse large B-cell lymphomas in mice. Cancer Cell 2005, 7, 445-455.
70. Sakajiri, S.; Kumagai, T.; Kawamata, N.; Saitoh, T.; Said, J.; Koeffler, H. Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines. Exp. Hematol. 2005, 33, 53-61.
71. Sanchez-Beato, M.; Sanchez-Aguilera, A.; Piris, M. A. Cell cycle deregulation in B-cell lymphomas. Blood 2003, 101, 1220-1235.
72. Sherr, C. J. The Pezcoller Lecture: Cancer cell cycles revisited. Cancer Res. 2000, 60, 3689-3695.
73. Sanchez-Beato, M.; Saez, A. I.; Navas, I. C.; Algara, P.; Mateo, M. S.; Villuendas, R.; Camacho, F.; Sanchez-Aguilera, A.; Sanchez, E.; Piris, M. A. Overall survival in aggressive B-cell lymphomas is dependent on the accumulation of alterations in p53, p16, and p27. Am. J. Pathol. 2001, 159, 205-213.
74. Ichikawa, A.; Kinoshita, T.; Watanabe, T.; Kato, H.; Nagai, H.; Tsushita, K.; Saito, H.; Hotta, T. Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma. N. Engl. J. Med. 1997, 337, 529-534.
75. Moller, M. B.; Ino, Y.; Gerdes, A. M.; Skjodt, K.; Louis, D. N.; Pedersen, N. T. Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma. Leukemia 1999, 13, 453-459.
76. Rao, P. H.; Houldsworth, J.; Dyomina, K.; Parsa, N. Z.; Cigudosa, J. C.; Louie, D. C.; Popplewell, L.; Offit, K.; Jhanwar, S. C.; Chaganti, R. S. K. Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood 1998, 92, 234-240.
77. Sanchez-Aguilera, A.; Sanchez-Beato, M.; Garcia, J. F.; Prieto, I.; Pollan, M.; Piris, M. A. p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways. Blood 2002, 99, 1411-1418.
78. 6-alkylguanine-DNA alkyltransferase. Prog. Nucleic Acid Res. Mol. Biol. 1995, 51, 167-223.
79. Jares, P.; Colomer, D.; Campo, E. Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat. Rev. Cancer 2007, 7, 750-762.
80. Witzig, T. E. Current treatment approaches for mantle-cell lymphoma. J. Clin. Oncol. 2005, 23, 6409-6414.
81. Lovec, H.; Grzeschiczek, A.; Kowalski, M. B.; Moroy, T. Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice. EMBO J. 1994, 13, 3487-3495.
82. Schraders, M.; Pfundt, R.; Straatman, H. M.; Janssen, I. M.; van Kessel, A. G.; Schoenmakers, E. F.; van Krieken, J. H.; Groenen, P. J. Novel chromosomal imbalances in mantle cell lymphoma detected by genome-wide array-based comparative genomic hybridization. Blood 2005, 105, 1686-1693.
83. Fernandez, V.; Hartmann, E.; Ott, G.; Campo, E.; Rosenwald, A. Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways. J. Clin. Oncol. 2005, 23, 6364-6369.
84. Liu, H.; Wang, J.; Epner, E. M. Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences. Blood 2004, 104, 2505-2513.
85. Hutter, G.; Scheubner, M.; Zimmermann, Y.; Kalla, J.; Katzenberger, T.; Hübler, K.; Roth, S.; Hiddemann, W.; Ott, G.; Dreyling, M. Differential effect of epigenetic alterations and genomic deletions of CDK inhibitors [p16(INK4a), p15(INK4b), p14(ARF)] in mantle cell lymphoma. Genes Chromosomes Cancer 2006, 45, 203-210.
86. Hernandez, L.; Fest, T.; Cazorla, M.; Teruya-Feldstein, J.; Bosch, F.; Peinado, M. A.; Piris, M. A.; Montserrat, E.; Cardesa, A.; Jaffe, E. S.; Campo, E.; Raffeld, M. p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphoma. Blood 1996, 87, 3351-3359.
87. Rizvi, M. A.; Evens, A. M.; Tallman, M. S.; Nelson, B. P.; Rosen, S. T. T-cell non-Hodgkin lymphoma. Blood 2006, 107, 1255-1264.
88. Willemze, R.; Kerl, H.; Sterry, W.; Berti, E.; Cerroni, L.; Chimenti, S.; Diaz-Perez, J. L.; Geerts, M. L.; Goos, M.; Knobler, R.; Ralfkiaer, E.; Santucci, M.; Smith, N.; Wechsler, J.; van Vloten, W. A.; Meijier, C. J. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997, 90, 354-371.
89. van Doorn, R.; Gruis, N. A.; Willemze, R.; van der Velden, P. A.; Tensen, C. P. Aberrant DNA methylation in cutaneous malignancies. Semin. Oncol. 2005, 32, 479-487.
90. Sommer, V. H.; Clemmensen, O. J.; Nielsen, O.; Wasik, M.; Lovato, P.; Brender, C.; Eriksen, K. W.; Woetmann, A.; Kaestel, C. G.; Nissen, M. H.; Ropke, C.; Skov, S.; Odum, N. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia 2004, 18, 1288-1295.
91. Lissy, N. A.; Davis, P. K.; Irwin, M.; Kaelin, W. G.; Dowdy, S. F. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature 2000, 407, 642-645.
92. Mann, B. S.; Johnson, J. R.; Cohen, M. H.; Justice, R.; Pazdur, R. FDA approval summary: Vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 2007, 12, 1247-1252.
93. 389IL-2 in leukemia and lymphoma cells by upregulation of IL-2R beta gene. Leuk. Res. 2002, 26, 1077-1083.
94. Piekarz, R. L.; Robey, R. W.; Zhan, Z.; Kayastha, G.; Sayah, A.; Abdeldaim, A. H.; Torrico, S.; Bates, S. E. T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. Blood 2004, 103, 4636-4643.
95. Schwering, I.; Bräuninger, A.; Klein, U.; Jungnickel, B.; Tinguely, M.; Diehl, V.; Hansmann, M. L.; Dalla-Favera, R.; Rajewsky, K.; Küppers, R. Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 2003, 101, 1505-1512.
96. Garcia, J. F.; Camacho, F. I.; Morente, M.; Fraga, M.; Montalbán, C.; Alvaro, T.; Bellas, C.; Castano, A.; Diez, A.; Flores, T.; Martin, C.; Martinez, M. A.; Mazorra, F.; Menarguez, J.; Mestre, M. J.; Mollejo, M.; Saez, A. I.; Sanchez, L.; Piris, M. A. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 2003, 101, 681-689.
97. Ushmorov, A.; Leithäuser, F.; Sakk, O.; Weinhaüsel, A.; Popov, S. W.; Möller, P.; Wirth, T. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood 2006, 107, 2493-2500.
98. Bachman, K. E.; Park, B. H.; Rhee, I.; Rajagopalan, H.; Herman, J. G.; Baylin, S. B.; Kinzler, K. W.; Vogelstein, B. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 2003, 3, 89-95.
99. Theil, J.; Laumen, H.; Marafioti, T.; Hummel, M.; Lenz, G.; Wirth, T.; Stein, H. Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood 2001, 97, 3191-3196.
100. Torlakovic, E.; Tierens, A.; Dang, H. D.; Delabie, J. The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease. Am. J. Pathol. 2001, 159, 1807-1814.
101. Ushmorov, A.; Ritz, O; Hummel, M.; Möller, P.; Stein, H.; Wirth, T. Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood 2004, 104, 3326-3334.
102. INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas. Blood 2004, 103, 2351-2357.
103. Murray, P. G.; Qiu, G. H.; Fu, L.; Waites, E. R.; Srivastava, G.; Heys, D.; Agathanggelou, A.; Latif, F.; Grundy, R. G.; Mann, J. R.; Starczynski, J.; Crocker, J.; Parkes, S. E.; Ambinder, R. F.; Young, L. S.; Tao, Q. Frequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin's lymphoma. Oncogene 2004, 23, 1326-1331.
104. Tzankov, A.; Zimpfer, A.; Lugli, A.; Krugmann, J.; Went, P.; Schraml, P.; Maurer, R.; Ascani, S.; Pileri, S.; Geley, S.; Dirnhofer, S. High-throughput tissue microarray analysis of G1-cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin E1. J. Pathol. 2003, 199, 201-207.
105. Tourigny, M. R.; Ursini-Siegel, J.; Lee, H.; Toellner, K. M.; Cunningham, A. M.; Franklin, D. S.; Ely, S.; Chen, M.; Qin, X. F.; Xiong, Y.; MacLennan, I. C. M.; Chen-Kiang, S. CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells. Immunity 2002, 17, 179-189.
106. Metivier, R.; Gallais, R.; Tiffoche, C.; Le Peron, C.; Jurkowska, R. Z.; Carmouche, R. P.; Ibberson, D.; Barath, P.; Demay, F.; Reid, G.; Benes, V.; Jeltsch, A.; Gannon, F.; Salbert, G. Cyclical DNA methylation of a transcriptionally active promoter. Nature 2008, 452, 45-50.
107. Lyko, F.; Brown, R. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst. 2005, 97, 1498-1506.
108. Jones, P. A.; Taylor, S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980, 20, 85-93.
109. Juttermann, R.; Li, E.; Jaenisch, R. Toxicity of 5-aza-2′- deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc. Natl. Acad. Sci. USA 1994, 91, 11797-11801.
110. Issa, J. P.; Gharibyan, V.; Cortes, J.; Jelinek, J. Morris, G.; Verstovsek, S.; Talpaz, M.; Garcia-Manero, G.; Kantarjian, H. M. Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J. Clin. Oncol. 2005, 23, 3948-3956.
111. Zhou, L.; Cheng, X.; Connolly, B. A.; Dickman, M. J.; Hurd, P. J.; Hornby, D. P. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 2002, 321, 591-599.
112. Herranz, M.; Martín-Caballero, J.; Fraga, M. F.; Ruiz-Cabello, J.; Flores, J. M.; Desco, M.; Marquez, V.; Esteller, M. The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma. Blood 2006, 107, 1174-1177.
113. Brueckner, B.; Boy, R. G.; Siedlecki, P.; Musch, T.; Kliem, H. C.; Zielenkiewicz, P.; Suhai, S.; Wiessler, M.; Lyko, F. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005, 65, 6305-6311.
114. WAF/Cip1 by distinct mechanisms. J. Biol. Chem. 1999, 274, 24250-24256.
115. McLaughlin, F.; La Thangue, N. B. Histone deacetylase inhibitors open new doors in cancer therapy. Biochem. Pharmacol. 2004, 68, 1139-1144.
116. Minucci, S.; Pelicci, P. G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 2006, 6, 38-51.
117. Hellebrekers, D. M. E. I.; Griffioen, A. W.; van Engeland, M. Dual targeting of epigenetic therapy in cancer. Biochim. Biophys. Acta 2007, 1775, 76-91.
118. Xiao, H.; Hasegawa, T.; Miyaishi, O.; Ohkusu, K.; Isobe, K. Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances promoter activity of p21WAF/CIP1 in p53-independent manner. Biochem. Biophys. Res. Commun. 1997, 237, 457-460.
119. Ju, R.; Muller, M. T. Histone deacetylase inhibitors activate p21WAF1 expression via ATM. Cancer Res. 2003, 63, 2891-2897.
120. 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, 2429-2440.
121. 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. J. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leucemia. Blood 2007, 109, 52-57.
122. Weiss, A. J.; Metter, G. E.; Nealon, T. F.; Keanan, J. P.; Ramirez, G.; Swaiminathan, A.; Fletcher, W. S.; Moss, S. E.; Manthei, R. W. Phase II study of 5-azacytidine in solid tumors. Cancer Treat. Rep. 1977, 61, 55-58.
123. Abele, R.; Clavel, M.; Dodion, P.; Bruntsch, U.; Gundersen, S.; Smyth, J.; Renard, J.; Van Glabbeke, M.; Pinedo, H. M. The EORTC Early Clinical Trials Cooperative Group experience with 5-aza-2′-deoxycytidine (NSC 127716) in patients with colo-rectal, head and neck, renal carcinomas and malignant melanomas. Eur. J. Cancer Clin. Oncol. 1987, 23, 1921-1924.
124. Samlowski, W. E.; Leachman, S. A.; Wade, M.; Cassidy, P.; Porter-Gill, P.; Busby, L.; Wheeler, R.; Boucher, K.; Fitzpatrick, F.; Jones, D. A.; Karpf, A. R. Evaluation of a 7-day continuous intravenous infusion of decitabine: inhibition of promoter-specific and global genomic DNA methylation. J. Clin. Oncol. 2005, 23, 3897-3905.
125. Schwartsmann, G.; Schunemann, H.; Gorini, C. N.; Ferreira-Filho, A. F.; Garbino, C.; Sabini, G.; Muse, I.; DiLeone, L.; Mans, D. R. A phase I trial of cisplatin plus decitabine, a new DNA-hypomethylating agent, in patients with advanced solid tumors and a follow-up early phase II evaluation in patients with inoperable non-small cell lung cancer. Invest. New Drugs 2000, 18, 83-91.
126. Gollob, J. A.; Sciambi, C. J.; Peterson, B. L.; Richmond, T.; Thoreson, M.; Moran, K.; Dressman, H. K.; Jelinek, J.; Issa, J. P. J. Phase I trial of sequential low-dose 5-aza-2′-deoxycytidine plus high-dose intravenous bolus interleukin-2 in patients with melanoma or renal cell carcinoma. Clin. Cancer Res. 2006, 12, 4619-4627.
127. Duvic, M.; Talpur, R.; Ni, X.; Zhang, G.; Hazarika, P.; Kelly, C.; Chiao, J. H.; Reilly, J. F.; Ricker, J. L.; Richon, V. M.; Frankel, S. R. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007, 109, 31-39.
128. Olsen, E. A.; Kim, Y. H.; Kuzel, T. M.; Pacheco, T. R.; Foss, F. M.; Parker, S.; Frankel, S. R.; Chen, C.; Ricker, J. L.; Arduino, J. M.; Duvic, M. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment-refractory cutaneous T-cell lymphoma. J. Clin. Oncol. 2007, 25, 3109-3115.
129. Byrd, J. C.; Shinn, C.; Ravi, R.; Willis, C. R.; Waselenko, J. K.; Flinn, I. W.; Dawson, N. A.; Grever, M. R. Depsipeptide (FR901228): a novel therapeutic agent with selective, in vitro activity against human B-cell chronic lymphocytic leukemia cells. Blood 1999, 94, 1401-1408.
130. Byrd, J. C.; Marcucci, G.; Parthun, M. R.; Xiao, J. J.; Klisovic, R. B.; Moran, M.; Lin, T. S.; Liu, S.; Sklenar, A. R.; Davis, M. E.; Lucas, D. M.; Fischer, B.; Shank, R.; Tejaswi, S. L.; Binkley, P.; Wright, J.; Chan, K. K.; Grever, M. R. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 2005, 105, 959-967.
131. Piekarz, R. L.; Robey, R.; Sandor, V.; Bakke, S.; Wilson, W. H.; Dahmoush, L.; Kingma, D. M.; Turner, M. L.; Altemus, R.; Bates, S. E. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood 2001, 98, 2865-2868.
132. Hess-Stumpp, H.; Bracker, T. U.; Henderson, D.; Politz, O. MS-275, a potent orally available inhibitor of histone deacetylases- The development of an anticancer agent. Int. J. Cell Biochem. Biol. 2007, 39, 1388-1405.
133. Ryan, Q. C.; Headlee, D.; Acharya, M.; Sparreboom, A.; Trepel, J. B.; Ye, J.; Figg, W. D.; Hwang, K.; Chung, E. J.; Murgo, A.; Melillo, G.; Elsayed, Y.; Monga, M.; Kalnitskiy, M.; Zwiebel, J.; Sausville, E. A. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J. Clin. Oncol. 2005, 23, 3912-3922.
134. Kell, J. Drug evaluation: MGCD-0103, a histone deacetylase inhibitor for the treatment of cancer. Curr. Opin. Investig. Drugs 2007, 8, 485-492.
135. Zain, J.; Rotter, A.; Weiss, L.; Forman, S.; Kirschbaum, M. H. Valproic
136. Yang, H.; Hoshino, K.; Sanchez-Gonzalez, B.; Kantarjian, H.; Garcia-Manero, G. Antileukemia activity of the combination of 5-aza-2′-deoxycytidine with valproic acid. Leuk. Res. 2005, 29, 739-748.
137. 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, 6361-6369.
138. Fantin, V. R.; Richon, V. M. Mechanisms of resistance to histone deacetylase inhibitors and their therapeutic implications. Clin. Cancer Res. 2007, 13, 7237-7242.