Histone deacetylase inhibitors in the treatment of hematological malignancies

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 6, 2011, Pages 519-527

  Petrella, A ^a   Fontanella, B ^a   Carratu A ^a   Bizzarro, V ^a   Rodriquez, M ^a   Parente, L ^a  

^a UNIVERSITY OF SALERNO   (Italy)

Author keywords

Hematological malignancies; Histone deacetylases; Histone deacetylases inhibitors

Indexed keywords

BELINOSTAT; DEPSIPEPTIDE; DX 275; ENTINOSTAT; HISTONE DEACETYLASE 1; MOCETINOSTAT; PANOBINOSTAT; PROMYELOCYTIC LEUKEMIA PROTEIN; RETINOIC ACID RECEPTOR ALPHA; ROMIDEPSIN; UNCLASSIFIED DRUG; VORINOSTAT;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC LEUKEMIA; ADVANCED CANCER; ANEMIA; ANOREXIA; APOPTOSIS; B CELL LYMPHOMA; CANCER CHEMOTHERAPY; CANCER RELAPSE; CELL CYCLE ARREST; CHROMATIN STRUCTURE; CHROMOSOME TRANSLOCATION; CHRONIC LYMPHATIC LEUKEMIA; DECREASED APPETITE; DIARRHEA; DRUG SAFETY; DRUG TOLERANCE; FATIGUE; FLUSHING; FOLLICULAR LYMPHOMA; HEMATOLOGIC MALIGNANCY; HISTONE ACETYLATION; HODGKIN DISEASE; HUMAN; HYPERCALCEMIA; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPOKALEMIA; HYPOPHOSPHATEMIA; IMMUNE RESPONSE; LEUKOPENIA; LYMPHOCYTOPENIA; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PRURITUS; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN LYMPHOMA; T CELL LYMPHOMA; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING;

BENZAMIDES; HEMATOLOGIC NEOPLASMS; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; HYDROXAMIC ACIDS; PEPTIDES, CYCLIC;

EID: 79959463506     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955711795843347     Document Type: Review

References (73)

1. Esteller, M. Cancer epigenomics: DNA methylomes and histonemodification maps. Nat. Rev. Genet., 2007, 4, 286-298.
2. Wang, G.G.; Allias, C.D. Chromating remodeling and cancer. Part I. Covalent histone modifications. Trends Mol. Med., 2007, 13, 363-372.
3. Yang, X.J.; Seto, E. The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat. Rev. Mol. Cell Biol., 2008, 9, 206-218.
4. Cang, S.; Ma, Y.; Liu, D. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. J. Hematol. Oncol., 2009, 2, 22.
5. Brosch, G.; Loidl, P.; Graessle, S. Histone modifications and chromatin dynamics: a focus on filamentous fungi. FEMS Microbiol. Rev., 2008, 32, 409-439.
6. Gregoretti, I.V.; Lee, Y.M.; Goodson, H.V. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol., 2004, 338, 17-31.
7. Verdin, E., Dequiedt, F., Kasler, H.G. Class II histone deacetylases: versatile regulators. Trends Genet., 2003, 19, 286-293.
8. 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, 194-202.
9. Gao, L.; Cueto, M.A.; Asselbergs, F.; Atadja, P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J. Biol. Chem., 2002, 277, 25748-25755.
10. Thiagalingam, S.; Cheng, K.H.; Lee, H.J.; Mineva, N.; Thiagalingam, A.; Ponte, J.F. Histone deacetylases: unique players in shaping the epigenetic histone code. Ann. NY Acad. Sci., 2003, 983, 84-100.
11. Glozak, M.A.; Sengupta, N.; Zhang, X.; Seto, E. Acetylation and deacetylation of non-histone proteins. Gene, 2005; 363, 15-23.
12. Singh, B.N.; Zhang, G.; Hwa, Y.L.; Li, J; Dowdy, S.C.; Jiang, S.W. Nonhistone protein acetylation as cancer therapy targets. Expert Rev. Anticancer Ther., 2010, 10, 935-954.
13. Tabe, Y.; Jin, L.; Contractor, R.; Gold, D.; Ruvolo, P.; Radke, S.; Xu, Y.; Tsutusmi-Ishii, Y.; Miyake, K.; Miyake, N.; Kondo, S.; Ohsaka, A.; Nagaoka, I.; Andreeff, M.; Konopleva, M. Novel role of HDAC inhibitors in AML1/ETO AML cells: activation of apoptosis and phagocytosis through induction of annexin A1. Cell Death Diff., 2007, 14, 1443-1456.
14. Petrella, A.; D'Acunto, W.; Rodriquez, M.; Festa, M.; Tosco, A; Bruno, I.; Terracciano, S.; Taddei, M.; Gomez Paloma, L.; Parente, L. Effects of FR235222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukemia cell lines: role of annexin A1. Eur. J. Cancer, 2008, 44, 740-49.
15. Mahlknecht, U.; Hoelzer, D. Histone acetylation modifiers in the pathogenesis of malignant disease. Mol. Med., 2000, 6, 623-44.
16. Cress, W.D.; Seto, E.; Histone deacetylases, transcriptional control, and cancer. J. Cell Physiol., 2000, 184, 1-16.
17. Prince, H.M.; Bishton, M.J.; Harrison, S.J. Clinical studies of histone deacetylase inhibitors. Clin. Cancer Res., 2009, 15, 3958-3969.
18. Redner, R.L.; Wang, J.; Liu, J.M. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood, 1999, 94, 417-428.
19. Minucci, S.; Nervi, C.; Lo Coco, F.; Pelicci, P.G. Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias? Oncogene, 2001, 20, 3110-3115.
20. Minucci, S.; Pelicci, P.G. Retinoid receptors in health and disease: co-regulators and the chromatin connection. Semin. Cell Dev. Biol., 1999, 10, 215-225.
21. 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.
22. Peterson, L.F.; Zhang, D.E. The 8;21 translocation in leukemogenesis. Oncogene, 2004, 23, 4255-4262.
23. Wang, J.; Hoshino, T.; Redner, R.L.; Kajigaya, S.; Liu, J.M.; ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc. Natl. Acad Sci. USA., 1998, 95, 10860-10865.
24. Liu, S.; Klisovic, R.B.; Vukosavljevic, T.; Yu, J.; Paschka, P.; Huynh, L.; Pang, J.; Neviani, P.; Liu, Z.; Blum, W.; Chan, K.K.; Perrotti, D.; Marcucci, G. Targeting AML1/ETO-histone deacetylase repressor complex: a novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cells. J. Pharmacol. Exp. Ther., 2007, 321, 953-960.
25. Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, EM.; Ferrara, F.; Bresciani, F.; Weisz, A.; de Lera, A.R.; Gronemeyer, H.; Altucci, L. Tumorselective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat. Med., 2005, 11, 77-84.
26. Shaffer, A.L.; Rosenwald, A.; Staudt, L.M. Lymphoid malignancies: the dark side of B-cell differentiation. Nat. Rev. Immunol., 2002, 2, 920-932.
27. Lemercier, S.; Brocard, M.P.; Puvion-Dutilleul, F.; Kao, H.Y; Albagli, O.; Khochbin, S. Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor. J. Biol. Chem., 2002, 277, 22045-22052.
28. Bereshchenko, O.R.; Gu, W.; Dalla-Favera, R. Acetylation inactivates the transcriptional repressor BCL6. Nat. Genet., 2002, 32, 606-613.
29. Ferrando, A.A.; Herblot, S.; Palomero, T.; Hansen, M.; Hoang, T.; Fox, E.A.; Look, A.T. Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia. Blood, 2004, 103, 1909-1911.
30. O'Neil, J.; Shank, J.; Cusson, N.; Murre, C.; Kelliher, M. TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/ HEB. Cancer Cell, 2004, 5, 587-596.
31. Richon, V.M.; Emiliani, S.; Verdin, E.; Webb, Y.; Breslow, R.; Rifkind, R.A.; Marks, P.A.; A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc. Natl. Acad. Sci. USA., 1998, 95, 3003-3007.
32. Marks, P.A.; Richon, V.M.; Rifkind, R.A. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J. Natl. Cancer Inst., 2000, 92, 1210-1216.
33. 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.
34. Duvic, M.; Talpur, R.; Ni, X.; Zhang, C.; 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.
35. 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.
36. Duvic, M.; Vu, J. Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma. Expert. Opin. Investig. Drugs, 2007, 16, 1111-1120.
37. 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.
38. Fantin, V.R.; Loboda, A.; Paweletz, C.P.; Hendrickson, R.C.; Pierce, J.W.; Roth, J.A. Constitutive activation of signal transducers and activators of transcription predicts Vorinostat resistance in cutaneous T-cell lymphoma. Cancer Res., 2008, 68, 3785-3794.
39. Kirschbaum, M.H.; Frankel, P.; Popplewell, L.; Zain, J.; Delioukina, M.L.; Pullarkat, V.; Matsuoka, D.; Pulone, B.; Rotter, A.J.; Espinoza-Delgado, I.; Nademanee, A.; Forman, S.J.; Gandara, D.; Newman, E. A phase 2 study of Vorinostat (suberoylanilide hydroxamic acid, SAHA) in relapsed or refractory indolent non Hodgkin lymphoma and Mantle Cell Lymphoma. J. Clin. Oncol., 2011, 29, 1198-1203.
40. 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 1 study of the histone deacetylase inhibitor Vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood, 2008, 111, 1060-1066.
41. Gimsing, P. Belinostat: a new broad acting antineoplastic histone deacetylase inhibitor. Expert Opin. Investig. Drugs, 2009, 18, 501-508.
42. Kapoor, S. Inhibition of HDAC6-dependent carcinogenesis: emerging, new therapeutic options besides belinostat. Int. J. Cancer, 2009, 124, 509.
43. Qian, X.; Ara, G.; Mills, E.; LaRochelle, W.J.; Lichenstein, H.S.; Jeffers, M. Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. Int. J. Cancer, 2008, 122, 1400-1410.
44. Gimsing, P.; Hansen, M.; Knudsen, L.M.; Knoblauch, P.; Christensen, I.J.; Ooi, C.E.; Buhl-Jensen, P.; A phase I clinical trial of the histone deacetylase inhibitor belinostat in patients with advanced hematological neoplasia. Eur. J. Haematol., 2008, 81, 1706.
45. Zain, J.M.; Foss, F.; Kelly, W.K.; DeBono, J.; Petrylak, D.; Narwal, A.; Neylon, E.; Blumenschein, G.; Lassen, U.; O'Connor, O. A. Final results of a phase I study of oral belinostat (PXD101) in patients with lymphoma. J. Clin. Oncol., (ASCO annual meeting), 2009, 27:15s (Suppl) [Abstract 8580].
46. Pohlman, B.; Advani, R.; Duvic, M,; Hymes, K.B.; Intragumtornchai, T.; Lekhakula, A.; Shpilberg, O.; Lerner, A.; Ben-Yehuda, D.; beylot-Barry, M.; Hillen, U.; Fagerberga, J.; Foss, F.M. Final Results of a Phase II Trial of Belinostat (PXD101) in Patients with Recurrent or Refractory Peripheral or Cutaneous TCell Lymphoma. 51st ASH Annual Meeting and Exposition, 2009 [Abstract 920]
47. George, P.; Bali, P.; Annavarapu, S.; Scuto, A.; Fiskus, W.; Guo, F.; Sigua, C.; Sondarva, G.; Moscinski, L.; Atadja, P.; Bhalla, K. Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood, 2005, 105, 1768-1776.
48. Hasegawa, H.; Yamada, Y.; Tsukasaki, K.; Mori, N.; Tsuruda, K.; Sasaki, D.; Usui, T.; Osaka, A.; Atogami, S.; Ishikawa, C.; Machijima, Y.; Sawada, S.; Hayashi, T.; Miyazaki, Y.; Kamihira, S. LBH589, a deacetylase inhibitor, induces apoptosis in adult Tcell leukemia/lymphoma cells via activation of a novel RAIDDcaspase-2 pathway. Leukemia, 2011, 25, 575-587.
49. Giles, F.; Fischer, T.; Cortes, J.; Garcia-Manero, G.; Beck, J.; Ravandi, F.; Masson, E.; Rae, P.; Laird, G.; Sharma, S.; Kantarjian, H.; Dugan, M.; Albitar, M.; Bhalla, K. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin. Cancer Res., 2006, 12, 4628-4635.
50. Sharma, S.; Vogelzang, N.J.; Beck, J.; Patnaik, A.; Mita, M.; Dugan, M.; Hwang, A.; Masson, Culver, K.W.; Prince, H. Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of LBH589, a novel deacetylase (DAC) inhibitor given intravenously on a new once weekly schedule. J. Clin. Oncol., 2007, 25, 18S(June(Suppl)) [14019].
51. Prince, H.M.; George, D.J.; Patnaik, A.; Mita, N.; Dugan, M.; Butterfoss, D.; Masson, E.; Culver, K.V,; Burris, H. A.; Beck, J. Phase study of oral LBH589, a novel deacetylase (DAC) inhibitor in advanced solid tumors and Non-Hodgkin's lymphoma J. Clin. Oncol., 2007, 25 [Abstract 3500].
52. Duvic, M.; Becker, J.C.; Dalle, S.; Vanaclocha, F.; Bernengo, M.G.; Lebbe, C.; Dummer, R.; Hirawat, S.; Zhang, L.; Marshood, M.; et al. Phase II Trial of Oral Panobinostat (LBH589) in Patients with Refractory Cutaneous T-Cell Lymphoma (CTCL). ASH Ann. Meet., 2008, 112, 1005.
53. Wolf, J.L.; Siegel, D.; Matous, J.; Lonial, S.; Goldschmidt, H.; Schmitt, S.; Vij, R.; De Malgalhaes-Silverman, M.; Abonour, R.; Jalaluddin, M.; Li, M.; Hazell, K.; Bourquelot, P.M.; Mateos, M.V.; Anderson, K.C.: Spencer, A.; Harousseau, J.L.; Bladé, J.A. Phase II Study of Oral Panobinostat (LBH589) in Adult Patients with Advanced Refractory Multiple Myeloma. ASH Annual Meeting., 2008, 112, 2774.
54. Konstantinopoulos, P.A.; Vandoros, G.P.; Papavassiliou, A.; G.FK228 (Depsipeptide): a HDAC inhibitor with pleiotropic antitumor activities. Cancer Chemother. Pharmacol., 2006, 58, 711-715.
55. Furumai, R.; Matsuyama, A.; Kobashi, N.; Lee, K.H.; Nishiyama, M.; Nakajima, H.; Tanaka, A.; Komatsu, Y.; Nishino, N.; Yoshida, M.; Horinouchi, S. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res., 2002, 62, 4916-4921.
56. Aron, J.L.; Parthun, M.R.; Marcucci, G.; Kitada, S.; Mone, A.P.; Davis, M.E.; Shen, T.; Murphy, T.; Wickham, J.; Kanakry, C.; Lucas, D.M.; Reed, J.C.; Grever, M.R.; Byrd, J.C. Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood, 2003, 102, 652-658
57. Kim, Y.; Whittaker, S.; Demierre, M.F.; Rook, A.H.; Lerner, A.; Duvic, M.; et al.; Clinically significant responses achieved with Romidepsin in treatment-refractory cutaneous T-cell lymphoma: final results from a phase 2B, International, Multicenter, Registration Study. Blood (ASH annual meeting abstracts), 2008, 112 [Abstract 263].
58. Bates, S.; Piekarz, R.; Wright, J.; Frye, R.; Figg, Sr. W.D.; Allen, A.L.; et al.; Final clinical results of a phase 2 NCI multicenter study of Romidepsin in recurrent cutaneous T-cell lymphoma (molecular analyses included). Blood (ASH annual meeting abstracts), 2008, 112 [Abstract 1568].
59. Whittaker, S.J.; Demierre, M.F.; Kim, E.J.; Rook, A.H.; Lerner, A.; Duvic, M.; Scarisbrick, J.; Reddy, S.; Robak, T.; Becker, J.C.; Samtsov, A.; McCulloch, W.; Kim, Y.H.; Final Results From a Multicenter, International, Pivotal Study of Romidepsin in Refractory Cutaneous T-Cell Lymphoma. J. Clin. Oncol., 2010, 8(29):4485-4491.
60. 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.
61. Klimek, V.M.; Fircanis, S.; Maslak, P.; Guernah, I.; Baum, M.; Wu, N.; Panageas, K.; Wright, J.J.; Pandolfi, P.P.; Nimer, S.D. Tolerability, pharmacodynamics, and pharmacokinetics studies of Depsipeptide (Romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes. Clin. Cancer Res., 2008, 14, 826-832.
62. Piekarz, R.; Wright, J.; Frye, R.; Allen, S.L.; Craig, M.; Geskin, L.; Results of a phase 2 NCI multicenter study of Romidepsin in patients with relapsed peripheral T-cell lymphoma (PTCL). Blood (ASH annual meeting abstracts), 2008, 112, 1567.
63. Odenike, O.M.; Alkan, S.; Sher, D.; Godwin, J.E.; Huo, D.; Brandt, S.J.; Green, M.; Xie, J.; Zhang, Y.; Vesole, D.H.; Stiff, P.; Wright, J.; Larson, R.A.; Stock, W. Histone deacetylase inhibitor Romidepsin has differential activity in core binding factor acute myeloid leukemia. Clin. Cancer Res., 2008, 14, 7095-7101.
64. Niesvizky, R.; Ely, S.; Mark, T.; Aggarwal, S.; Gabrilove, J.L.; Wright, J.J.; Chen-Kiang, S,.; Sparano, J.A. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma. Cancer, 2011, 117, 336-342.
65. Fournel, M.; Bonfils, C.; Hou, Y.; Yan, P.T.; Trachy-Bourget, M.C.; Kalita, A.; Liu, J.; Lu, A.H.; Zhou, N.Z.; Robert, M.F.; Gillespie, J.; Wang, J.J.; Ste-Croix, H.; Rahil, J.; Lefebvre, S.; Moradei, O.; Delorme, D.; Macleod, A.R.; Besterman, J.M.; Li, Z. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol. Cancer Ther., 2008, 7, 759-768.
66. El-Khoury, V.; Moussay, E.; Janji, B.; Palissot, V.; Aouali, N.; Brons, N.H.; Van Moer, K.; Pierson, S.; Van Dyck, E.; Berchem, G. The histone deacetylase inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic leukemia cells through a mitochondria-mediated caspase activation cascade. Mol. Cancer Ther., 2010, 9, 1349-1360
67. Garcia-Manero, G.; Assouline, S.; Cortes, J.; Estrov, Z.; Kantarjian, H.; Yang, H.; Newsome, WM.; Miller, W.H. Jr, Rousseau, C.; Kalita, A.; Bonfils, C.; Dubay, M.; Patterson, T.A.; Li, Z.; Besterman, J.M.; Reid, G.; Laille, E.; Martell, R.E.; Minden, M. Phase 1 study of theoralisotype specific histone deacetylase inhibitor MGCD0103 in leukemia. Blood, 2008, 112, 981-989.
68. Bociek, R.G.; Kuruvilla, J.; Pro, B.; Wedgwood, A.; Li, Z.; Drouin, M.; Patterson, T.; Ward, R.; Martell, R.E.; Younes, A. Isotype selective histone deacetylase (HDAC) inhibitor MGCD0103 demonstrates clinical activity and safety in patients with relapsed/refractory classical Hodgkin lymphoma (HL). J. Clin. Oncol., 2008, 26, [Abstract 8507].
69. Stimson, L.; Wood, V.; Khan, O.; Fotheringham, S.; La Thangue NB. HDAC inhibitor based therapies and haematological malignancy. Ann. Oncol., 2009, 20, 1293-1302.
70. Martell, R.E.; Younes, A.; Assouline, S.E.; Rizzieri, D.; Fox S.; Drouin, M.A.; Wilhelm, J.; Mehran, M.; Besterman J.M.; Van Der Jagt, R.C.H. Phase 2 Study of MGCD0103 in Patients with Relapsed Follicular Lymphoma (FL): Study reinitiation and Update of Clinical Efficacy and Safety. J. Clin. Oncol., (ASCO annual meeting 2010), 2010, [Abstract ID 8086].
71. Hess-Stumppk, 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. Biochem. Cell Biol., 2007, 39, 1388-1405.
72. Khaskhely, N.M.; Buglio, D.; Shafer, J.; Bollard, C.M.; Younes, A. The histone deacetylase (HDAC) inhibitor entinostat (SNDX-275) targets hodgkin lymphoma through a dual mechanism of immune modulation and apoptosis induction. ASH Annual Meeting Abstracts., 2009, 114, 1562.
73. Gojo, I.; Jiemjit, A.; Trepel, J.B.; Sparreboom, A.; Figg, W.D.; Rollins, S.; Tidwell, M.L.; Greer, J.; Chung, E.J.; Lee, M.J.; Gore, S.D; Sausville, E.A.; Zwiebel, J.; Karp, J.E. Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood, 2007, 109, 2781-2790.