Table of Contents Author Guidelines Submit a Manuscript
Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 148046, 9 pages
http://dx.doi.org/10.1155/2011/148046
Review Article

The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias

Pediatric Oncology and Hematology “Lalla Seràgnoli” Unit, Department of Pediatrics, University of Bologna, 40137 Bologna, Italy

Received 11 July 2010; Revised 15 November 2010; Accepted 9 December 2010

Academic Editor: Christian Seiser

Copyright © 2011 Riccardo Masetti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Ravindranath, “Recent advances in pediatric acute lymphoblastic and myeloid leukemia,” Current Opinion in Oncology, vol. 15, no. 1, pp. 23–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. C. H. Pui, M. Schrappe, R. C. Ribeiro, and C. M. Niemeyer, “Childhood and adolescent lymphoid and myeloid leukemia,” American Society of Hematology. Education Program, pp. 118–145, 2004. View at Google Scholar · View at Scopus
  3. V. Conter, M. Aricò, and M. Aricò, “Long-term results of the Italian association of pediatric hematology and oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia,” Leukemia, vol. 24, no. 2, pp. 255–264, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. M. Aricò, M. G. Valsecchi, and M. G. Valsecchi, “Long-term results of the AIEOP-ALL-95 trial for childhood acute lymphoblastic leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster-based chemotherapy,” Journal of Clinical Oncology, vol. 26, no. 2, pp. 283–289, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. A. Pession, R. Rondelli, and R. Rondelli, “Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols,” Leukemia, vol. 19, no. 12, pp. 2043–2053, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. G. Tallen, R. Ratei, and R. Ratei, “Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90,” Journal of Clinical Oncology, vol. 28, no. 14, pp. 2339–2347, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. J. Abrahamsson, N. Clausen, and N. Clausen, “Improved outcome after relapse in children with acute myeloid leukaemia,” British Journal of Haematology, vol. 136, no. 2, pp. 229–236, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. G. J. L. Kaspers and C. N. Zwaan, “Pediatric acute myeloid leukemia: towards high-quality cure of all patients,” Haematologica, vol. 92, no. 11, pp. 1519–1532, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. P. Brown, S. P. Hunger, F. O. Smith, W. L. Carroll, and G. H. Reaman, “Novel targeted drug therapies for the treatment of childhood acute leukemia,” Expert Review of Hematology, vol. 2, no. 2, pp. 145–158, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. Y. Oki and J. P. Issa, “Review: recent clinical trials in epigenetic therapy,” Reviews on Recent Clinical Trials, vol. 1, no. 2, pp. 169–182, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. G. Kouraklis and S. Theocharis, “Histone deacetylase inhibitors and anticancer therapy,” Current Medicinal Chemistry, vol. 2, no. 4, pp. 477–484, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Timmermann, H. Lehrmann, A. Polesskaya, and A. Harel-Bellan, “Histone acetylation and disease,” Cellular and Molecular Life Sciences, vol. 58, no. 5-6, pp. 728–736, 2001. View at Google Scholar · View at Scopus
  13. P. A. Marks and W. S. Xu, “Histone deacetylase inhibitors: potential in cancer therapy,” Journal of Cellular Biochemistry, vol. 107, no. 4, pp. 600–608, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. M. A. Glozak and E. Seto, “Histone deacetylases and cancer,” Oncogene, vol. 26, no. 37, pp. 5420–5432, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. R. P. Warrell Jr., L. Z. He, V. Richon, E. Calleja, and P. P. Pandolfi, “Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase,” Journal of the National Cancer Institute, vol. 90, no. 21, pp. 1621–1625, 1998. View at Google Scholar · View at Scopus
  16. R. J. Lin, L. Nagy, S. Inoue, W. Shao, W. H. Miller, and R. M. Evans, “Role of the histone deacetylase complex in acute promyelocytic leukaemia,” Nature, vol. 391, no. 6669, pp. 811–814, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. F. Grignani, S. De Matteis, and S. De Matteis, “Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia,” Nature, vol. 391, no. 6669, pp. 815–818, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. I. Klisovic, E. A. Maghraby, and E. A. Maghraby, “Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells,” Leukemia, vol. 17, no. 2, pp. 350–358, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. S. Liu, R. B. Klisovic, and R. B. Klisovic, “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,” Journal of Pharmacology and Experimental Therapeutics, vol. 321, no. 3, pp. 953–960, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. A. M. Dorrance, S. Liu, and S. Liu, “Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations,” Journal of Clinical Investigation, vol. 116, no. 10, pp. 2707–2716, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. M. Paris, M. Porcelloni, M. Binaschi, and D. Fattori, “Histone deacetylase inhibitors: from bench to clinic,” Journal of Medicinal Chemistry, vol. 51, no. 6, pp. 1505–1529, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. A. Al-Janadi, S. R. Chandana, and B. A. Conley, “Histone deacetylation: an attractive target for cancer therapy?” Drugs in R and D, vol. 9, no. 6, pp. 369–383, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. A. L. Abujamra, M. P. dos Santos, R. Roesler, G. Schwartsmann, and A. L. Brunetto, “Histone deacetylase inhibitors: a new perspective for the treatment of leukemia,” Leukemia Research, vol. 34, no. 6, pp. 687–695, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. S. D. Gore, S. Baylin, and S. Baylin, “Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms,” Cancer Research, vol. 66, no. 12, pp. 6361–6369, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. G. Garcia-Manero, H. M. Kantarjian, and H. M. Kantarjian, “Phase 1/2 study of the combination of 5-aza-2-deoxycytidine with valproic acid in patients with leukemia,” Blood, vol. 108, no. 10, pp. 3271–3279, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. V. M. Richon, J. Garcia-Vargas, and J. S. Hardwick, “Development of vorinostat: current applications and future perspectives for cancer therapy,” Cancer Letters, vol. 280, no. 2, pp. 201–210, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. L. M. Butler, D. B. Agus, and D. B. Agus, “Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo,” Cancer Research, vol. 60, no. 18, pp. 5165–5170, 2000. View at Google Scholar · View at Scopus
  28. N. Batty, G. G. Malouf, and J. P. J. Issa, “Histone deacetylase inhibitors as anti-neoplastic agents,” Cancer Letters, vol. 280, no. 2, pp. 192–200, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. J. A. Vrana, R. H. Decker, and R. H. Decker, “Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-x(L), c-Jun, and p21(CIP1), but independent of p53,” Oncogene, vol. 18, no. 50, pp. 7016–7025, 1999. View at Google Scholar · View at Scopus
  30. H. G. Einsiedel, L. Kawan, C. Eckert, O. Witt, I. Fichtner, G. Henze, and K. Seeger, “Histone deacetylase inhibitors have antitumor activity in two NOD/SCID mouse models of B-cell precursor childhood acute lymphoblastic leukemia,” Leukemia, vol. 20, no. 8, pp. 1435–1436, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. G. J. Leclerc, C. Mou, G. M. Leclerc, A. M. Mian, and J. C. Barredo, “Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy,” Leukemia, vol. 24, no. 3, pp. 552–562, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. L. Z. He, T. Tolentino, and T. Tolentino, “Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia,” Journal of Clinical Investigation, vol. 108, no. 9, pp. 1321–1330, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. G. Garcia-Manero, H. Yang, and H. Yang, “Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes,” Blood, vol. 111, no. 3, pp. 1060–1066, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. M. Fouladi, J. R. Park, and J. R. Park, “Pediatric phase I trial and pharmacokinetic study of vorinostat: a Children's Oncology Group phase I consortium report,” Journal of Clinical Oncology, vol. 28, no. 22, pp. 3623–3629, 2010. View at Publisher · View at Google Scholar · View at PubMed
  35. M. J. Burke, Decitabine, Vorinostat, and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma That Has Relapsed or Not Responded to Treatment, http://clinicaltrials.gov/ct2/show/NCT00882206?term=VORINOSTAT+AND+leukemia&rank=6.
  36. G. Garcia-Manero, Phase II Study of Idarubicin, Cytarabine, and Vorinostat With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), http://clinicaltrials.gov/ct2/show/NCT00656617?term=VORINOSTAT+AND+leukemia&rank=20.
  37. M. Göttlicher, S. Minucci, and S. Minucci, “Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells,” EMBO Journal, vol. 20, no. 24, pp. 6969–6978, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. O. H. Krämer, P. Zhu, and P. Zhu, “The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2,” EMBO Journal, vol. 22, no. 13, pp. 3411–3420, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. R. Tonelli, R. Sartini, and R. Sartini, “G1 cell-cycle arrest and apoptosis by histone deacetylase inhibition in MLL-AF9 acute myeloid leukemia cells is p21 dependent and MLL-AF9 independent,” Leukemia, vol. 20, no. 7, pp. 1307–1310, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. A. Insinga, S. Monestiroli, and S. Monestiroli, “Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway,” Nature Medicine, vol. 11, no. 1, pp. 71–76, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. T. Siitonen, P. Koistinen, and E. R. Savolainen, “Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27 in acute myeloblastic leukemia cells,” Leukemia Research, vol. 29, no. 11, pp. 1335–1342, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. B. Sanchez-Gonzalez, H. Yang, C. Bueso-Ramos, K. Hoshino, A. Quintas-Cardama, V. M. Richon, and G. Garcia-Manero, “Antileukemia activity of the combination of an anthracycline with a histone deacetylase inhibitor,” Blood, vol. 108, no. 4, pp. 1174–1182, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. H. Yang, K. Hoshino, B. Sanchez-Gonzalez, H. Kantarjian, and G. Garcia-Manero, “Antileukemia activity of the combination of 5-aza-2-deoxycytidine with valproic acid,” Leukemia Research, vol. 29, no. 7, pp. 739–748, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. A. Kuendgen, S. Knipp, and S. Knipp, “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,” Annals of Hematology, Supplement, vol. 84, no. 13, supplement, pp. 61–66, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. G. Bug, M. Ritter, and M. Ritter, “Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia,” Cancer, vol. 104, no. 12, pp. 2717–2725, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. A. O. Soriano, H. Yang, and H. Yang, “Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome,” Blood, vol. 110, no. 7, pp. 2302–2308, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. S. Minucci and P. G. Pelicci, “Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer,” Nature Reviews Cancer, vol. 6, no. 1, pp. 38–51, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. R. R. Rosato, J. A. Almenara, and S. Grant, “The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1,” Cancer Research, vol. 63, no. 13, pp. 3637–3645, 2003. View at Google Scholar · View at Scopus
  49. C. Nishioka, T. Ikezoe, J. Yang, S. Takeuchi, H. Phillip Koeffler, and A. Yokoyama, “MS-275, a novel histone deacetylase inhibitor with selectivity against HDAC1, induces degradation of FLT3 via inhibition of chaperone function of heat shock protein 90 in AML cells,” Leukemia Research, vol. 32, no. 9, pp. 1382–1392, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. C. Nishioka, T. Ikezoe, J. Yang, H. P. Koeffler, and A. Yokoyama, “Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells,” Leukemia, vol. 22, no. 12, pp. 2159–2168, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. S. C. Maggio, R. R. Rosato, and R. R. Rosato, “The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells,” Cancer Research, vol. 64, no. 7, pp. 2590–2600, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Jaboin, J. Wild, and J. Wild, “MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors,” Cancer Research, vol. 62, no. 21, pp. 6108–6115, 2002. View at Google Scholar · View at Scopus
  53. I. Gojo, A. Jiemjit, and A. Jiemjit, “Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias,” Blood, vol. 109, no. 7, pp. 2781–2790, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. A. Batova, L. E. Shao, and L. E. Shao, “The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines,” Blood, vol. 100, no. 9, pp. 3319–3324, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. A. Aviram, Y. Zimrah, M. Shaklai, A. Nudelman, and A. Rephaeli, “Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL-60 leukemic cell line,” International Journal of Cancer, vol. 56, no. 6, pp. 906–909, 1994. View at Google Scholar · View at Scopus
  56. T. Kasukabe, A. Rephaeli, and Y. Honma, “An anti-cancer derivative of butyric acid (pivalyloxymethyl butyrate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells,” British Journal of Cancer, vol. 75, no. 6, pp. 850–854, 1997. View at Google Scholar · View at Scopus
  57. A Pilot Study of Pivanex in Patients With Chronic Lymphocytic Leukemi, http://clinicaltrials.gov/ct2/show/NCT00083473?term=AN-9&rank=1.
  58. A Pilot Study of Pivanex in Patients With Malignant Melanoma, http://clinicaltrials.gov/ct2/show/NCT00087477?term=AN-9&rank=2.
  59. Comparative Trial of Pivanex and Docetaxel Vs Docetaxel Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer, http://clinicaltrials.gov/ct2/show/NCT00073385?term=AN-9&rank=3.
  60. V. Guerini, V. Barbui, and V. Barbui, “The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2,” Leukemia, vol. 22, no. 4, pp. 740–747, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. A. Rambaldi, C. M. Dellacasa, and C. M. Dellacasa, “A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms,” British Journal of Haematology, vol. 150, no. 4, pp. 446–455, 2010. View at Publisher · View at Google Scholar · View at PubMed
  62. A. Rambaldi, Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera (PV), http://clinicaltrials.gov/ct2/show/NCT00928707?term=NCT00928707&rank=1.
  63. V. Barbetti, A. Gozzini, and A. Gozzini, “Selective anti-leukaemic activity of low-dose histone deacetylase inhibitor ITF2357 on AML1/ETO-positive cells,” Oncogene, vol. 27, no. 12, pp. 1767–1778, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. R. L. Piekarz, R. Frye, and R. Frye, “Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma,” Journal of Clinical Oncology, vol. 27, no. 32, pp. 5410–5417, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. “StatBite: FDA oncology drug product approvals in 2009,” Journal of the National Cancer Institute, vol. 102, no. 4, p. 219, 2010.
  66. H. Kosugi, M. Ito, and M. Ito, “In vivo effects of a histone deacetylase inhibitor, FK228, on human acute promyelocytic leukemia in NOD/Shi-scid/scid mice,” Japanese Journal of Cancer Research, vol. 92, no. 5, pp. 529–536, 2001. View at Google Scholar · View at Scopus
  67. J. C. Byrd, G. Marcucci, and G. Marcucci, “A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia,” Blood, vol. 105, no. 3, pp. 959–967, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. V. M. Klimek, S. Fircanis, and S. Fircanis, “Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (Romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes,” Clinical Cancer Research, vol. 14, no. 3, pp. 826–832, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. G. Garcia-Manero, S. Assouline, and S. Assouline, “Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia,” Blood, vol. 112, no. 4, pp. 981–989, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. M. Fournel, C. Bonfils, and C. Bonfils, “MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo,” Molecular Cancer Therapeutics, vol. 7, no. 4, pp. 759–768, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. A. A. Lane and B. A. Chabner, “Histone deacetylase inhibitors in cancer therapy,” Journal of Clinical Oncology, vol. 27, no. 32, pp. 5459–5468, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. A. Scuto, M. Kirschbaum, and M. Kirschbaum, “The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph acute lymphoblastic leukemia cells,” Blood, vol. 111, no. 10, pp. 5093–5100, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. F. Giles, T. Fischer, and T. Fischer, “A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies,” Clinical Cancer Research, vol. 12, no. 15, pp. 4628–4635, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus