Novel approaches to the treatment of sickle cell disease: The potential of histone deacetylase inhibitors

Expert Review of Hematology

Volumn 5, Issue 3, 2012, Pages 303-311

  Okam, Maureen M ^a   Ebert, Benjamin L ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

epigenetics; fetal hemoglobin; histone deacetylase inhibitors; hydroxyurea; panobinostat; sickle cell disease; vorinostat

Indexed keywords

2,2 DIMETHYLBUTYRATE; 4 PHENYLBUTYRIC ACID; 6 (1,3 DIOXO 1H,3H BENZO[DE]ISOQUINOLIN 2 YL) N HYDROXYHEXANAMIDE; ANTIANEMIC AGENT; APICIDIN; ARGININE BUTYRIC ACID; AZACITIDINE; BETA GLOBIN; BUTYRIC ACID DERIVATIVE; ENTINOSTAT; GAMMA GLOBIN; HELMINTHOSPORIUM CARBONUM TOXIN; HEMOGLOBIN A; HEMOGLOBIN F; HEMOGLOBIN S; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HQK 1001; HYDROXYUREA; POMALIDOMIDE; RECOMBINANT ERYTHROPOIETIN; ROMIDEPSIN; SIRTUIN; TRAPOXIN; TRICHOSTATIN A; UNCLASSIFIED DRUG;

BRAZIL; CHROMATIN ASSEMBLY AND DISASSEMBLY; CONTINUOUS INFUSION; DRUG APPROVAL; DRUG MECHANISM; DRUG SCREENING; ENZYME ACTIVITY; ERYTHROPOIESIS; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; HYPERHEMOGLOBINEMIA; LOW DRUG DOSE; MULTICENTER STUDY (TOPIC); NEWBORN ANEMIA; NONHUMAN; OXYGEN AFFINITY; PERINATAL PERIOD; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN POLYMERIZATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SAUDI ARABIA; SICKLE CELL ANEMIA; TRANSCRIPTION REGULATION;

ANEMIA, SICKLE CELL; ANIMALS; ANTISICKLING AGENTS; FETAL HEMOGLOBIN; HEMOGLOBIN, SICKLE; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXYUREA;

EID: 84863801973     PISSN: 17474086     EISSN: 17474094     Source Type: Journal    
DOI: 10.1586/ehm.12.20     Document Type: Review

References (88)

1. Sickle Cell Anaemia: REPORT by Secretariat. In: FIFTY-Ninth World Health Assembly. WHO, Geneva, Switzerland, 1-3 (2006).
2. Brousseau DC, Panepinto JA, Nimmer M, Hoffmann RG. The number of people with sickle-cell disease in the United States: National and state estimates. Am. J. Hematol. 85(1), 77-78 (2010).
3. Platt OS, Brambilla DJ, Rosse WF et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N. Engl. J. Med. 330(23), 1639-1644 (1994).
4. Steinberg MH, Lu ZH, Barton FB, Terrin ML, Charache S, Dover GJ. Fetal hemoglobin in sickle cell anemia: Determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood 89(3), 1078-1088 (1997).
5. Steinberg MH, Barton F, Castro O et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment. JAMA 289(13), 1645-1651 (2003).
6. Steinberg MH, McCarthy WF, Castro O et al.; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-Up. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am. J. Hematol. 85(6), 403-408 (2010).
7. Voskaridou E, Christoulas D, Bilalis A et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: Results of a 17-year, single-center trial (LaSHS). Blood 115(12), 2354-2363 (2010).
8. Okpala I. Leukocyte adhesion and the pathophysiology of sickle cell disease. Curr. Opin. Hematol. 13(1), 40-44 (2006).
9. Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood 110(6), 2166-2172 (2007).
10. Kato GJ, Martyr S, Blackwelder WC et al. Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality. Br. J. Haematol. 130(6), 943-953 (2005).
11. Watson J. The significance of the paucity of sickle cells in newborn Negro infants. Am. J. Med. Sci. 215(4), 419-423 (1948).
12. Herman EC Jr, Conley CL. Hereditary persistence of fetal hemoglobin. A family study. Am. J. Med. 29, 9-17 (1960).
13. Hutz MH, Salzano FM, Adams J. HbF levels, longevity of homozygotes and clinical course of sickle cell anemia in Brazil. Am. J. Med. Genet. 14(4), 669-676 (1983).
14. Kutlar A, Hattori Y, Bakioglu I, Kutlar F, Kamel K, Huisman TH. Hematological observations on Arabian SS patients with a homozygosity or heterozygosity for a beta S chromosome with haplotype #31. Hemoglobin 9(6), 545-557 (1985).
15. Platt OS, Thorington BD, Brambilla DJ et al. Pain in sickle cell disease. Rates and risk factors. N. Engl. J. Med. 325(1), 11-16 (1991).
16. Bertles JF, Rabinowitz R, Döbler J. Hemoglobin interaction: Modification of solid phase composition in the sickling phenomenon. Science 169(3943), 375-377 (1970).
17. Bookchin RM, Nagel RL, Balazs T. Role of hybrid tetramer formation in gelation of haemoglobin S. Nature 256(5519), 667-668 (1975).
18. Nagel RL, Bookchin RM, Johnson J et al. Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S. Proc. Natl Acad. Sci. USA 76(2), 670-672 (1979).
19. Bunn HF, Forget BG. Hemoglobin: MOLECULAR, Genetic and Clinical Aspects. Dyson J (Ed.). WB Saunders Company, PA, USA (1986).
20. Orringer EP, Blythe DS, Johnson AE, Phillips G Jr, Dover GJ, Parker JC. Effects of hydroxyurea on hemoglobin F and water content in the red blood cells of dogs and of patients with sickle cell anemia. Blood 78(1), 212-216 (1991).
21. Adragna NC, Fonseca P, Lauf PK. Hydroxyurea affects cell morphology, cation transport, and red blood cell adhesion in cultured vascular endothelial cells. Blood 83(2), 553-560 (1994).
22. Letvin NL, Linch DC, Beardsley GP, McIntyre KW, Nathan DG. Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N. Engl. J. Med. 310(14), 869-873 (1984).
23. Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J. Clin. Invest. 74(2), 652-656 (1984).
24. Charache S, Dover GJ, Moore RD et al. Hydroxyurea: Effects on hemoglobin F production in patients with sickle cell anemia. Blood 79(10), 2555-2565 (1992).
25. Veith R, Galanello R, Papayannopoulou T, Stamatoyannopoulos G. Stimulation of F-cell production in patients with sickle-cell anemia treated with cytarabine or hydroxyurea. N. Engl. J. Med. 313(25), 1571-1575 (1985).
26. Charache S, Terrin ML, Moore RD et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N. Engl. J. Med. 332(20), 1317-1322 (1995).
27. Charache S, Barton FB, Moore RD et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 75(6), 300-326 (1996).
28. Stamatoyannopoulos G, Veith R, Galanello R, Papayannopoulou T. HbF production in stressed erythropoiesis: Observations and kinetic models. Ann. NY Acad. Sci. 445, 188-197 (1985).
29. Alter BP, Rappeport JM, Huisman TH, Schroeder WA, Nathan DG. Fetal erythropoiesis following bone marrow transplantation. Blood 48(6), 843-853 (1976).
30. DeSimone J, Biel M, Heller P. Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress. Blood 60(2), 519-523 (1982).
31. Veith R, Papayannopoulou T, Kurachi S, Stamatoyannopoulos G. Treatment of baboon with vinblastine: Insights into the mechanisms of pharmacologic stimulation of HbF in the adult. Blood 66(2), 456-459 (1985).
32. Gabbianelli M, Testa U, Massa A et al. HbF reactivation in sibling BFU-E colonies: Synergistic interaction of kit ligand with low-dose dexamethasone. Blood 101(7), 2826-2832 (2003).
33. DeSimone J, Heller P, Hall L, Zwiers D. 5-azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc. Natl Acad. Sci. USA 79(14), 4428-4431 (1982).
34. Charache S, Dover G, Smith K, Talbot CC Jr, Moyer M, Boyer S. Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex. Proc. Natl Acad. Sci. USA 80(15), 4842-4846 (1983).
35. Koshy M, Dorn L, Bressler L et al. 2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. Blood 96(7), 2379-2384 (2000).
36. DeSimone J, Koshy M, Dorn L et al. Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. Blood 99(11), 3905-3908 (2002).
37. Saunthararajah Y, Hillery CA, Lavelle D et al. Effects of 5-aza-2́-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood 102(12), 3865-3870 (2003).
38. Perrine SP, Miller BA, Faller DV et al. Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with HbSS and beta thalassemia. Blood 74(1), 454-459 (1989).
39. Perrine SP, Rudolph A, Faller DV et al. Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. Proc. Natl Acad. Sci. USA 85(22), 8540-8542 (1988).
40. Constantoulakis P, Knitter G, Stamatoyannopoulos G. On the induction of fetal hemoglobin by butyrates: In vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5-AzaC and AraC. Blood 74(6), 1963-1971 (1989).
41. Bunn HF. Induction of fetal hemoglobin in sickle cell disease. Blood 93(6), 1787-1789 (1999).
42. Perrine SP, Ginder GD, Faller DV et al. A short-term trial of butyrate to stimulate fetal-globin-gene expression in the beta-globin disorders. N. Engl. J. Med. 328(2), 81-86 (1993).
43. Dover GJ, Brusilow S, Charache S. Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate. Blood 84(1), 339-343 (1994).
44. Kutlar A, Inati A, Taher AT et al. A Phase 2 Clinical Study of HQK-1001 (2,2-dimethylbutyrate, sodium salt), a fetal hemoglobin inducer, in patients with sickle cell disease. Blood, 118 (2011).
45. Goldberg MA, Brugnara C, Dover GJ, Schapira L, Charache S, Bunn HF. Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N. Engl. J. Med. 323(6), 366-372 (1990).
46. Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW. Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N. Engl. J. Med. 328(2), 73-80 (1993).
47. 34+ cells. J. Clin. Investig. 118(1), 248-258 (2008).
48. Meiler SE, Wade M, Kutlar F et al. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood 118(4), 1109-1112 (2011).
49. Wiech NL, Fisher JF, Helquist P, Wiest O. Inhibition of histone deacetylases: A pharmacological approach to the treatment of non-cancer disorders. Curr. Top. Med. Chem. 9(3), 257-271 (2009).
50. De Ruijter AJ, Van Gennip AH, Caron HN, Kemp S, Van Kuilenburg AB. Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochem. J. 370(Pt 3), 737-749 (2003).
51. Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J. Mol. Biol. 338(1), 17-31 (2004).
52. Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: Versatile regulators. Trends Genet. 19(5), 286-293 (2003).
53. Zhang Y, Gilquin B, Khochbin S, Matthias P. Two catalytic domains are required for protein deacetylation. J. Biol. Chem. 281(5), 2401-2404 (2006).
54. Sauve AA, Wolberger C, Schramm VL, Boeke JD. The biochemistry of sirtuins. Annu. Rev. Biochem. 75, 435-465 (2006).
55. Riggs MG, Whittaker RG, Neumann JR, Ingram VM. n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 268(5619), 462-464 (1977).
56. Boffa LC, Vidali G, Mann RS, Allfrey VG. Suppression of histone deacetylation in vivo and in vitro by sodium butyrate. J. Biol. Chem. 253(10), 3364-3366 (1978).
57. Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J. Biol. Chem. 265(28), 17174-17179 (1990).
58. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: Molecular mechanisms of action. Oncogene 26(37), 5541-5552 (2007).
59. Ma X, Ezzeldin HH, Diasio RB. Histone deacetylase inhibitors: Current status and overview of recent clinical trials. Drugs 69(14), 1911-1934 (2009).
60. Wagner JM, Hackanson B, Lübbert M, Jung M. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin. Epigenetics 1(3-4), 117-136 (2010).
61. Wright JM, Zeitlin PL, Cebotaru L, Guggino SE, Guggino WB. Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol. Genomics 16(2), 204-211 (2004).
62. Gondcaille C, Depreter M, Fourcade S et al. Phenylbutyrate up-regulates the adrenoleukodystrophy-related gene as a nonclassical peroxisome proliferator. J. Cell Biol. 169(1), 93-104 (2005).
63. Minetti GC, Colussi C, Adami R et al. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat. Med. 12(10), 1147-1150 (2006).
64. Forsberg EC, Downs KM, Christensen HM, Im H, Nuzzi PA, Bresnick EH. Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain. Proc. Natl Acad. Sci. USA 97(26), 14494-14499 (2000).
65. Bradner JE, Mak R, Tanguturi SK et al. Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease. Proc. Natl Acad. Sci. USA 107(28), 12617-12622 (2010).
66. Fathallah H, Atweh GF. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am. Soc. Hematol. Educ. Program 58-62 (2006).
67. McCaffrey PG, Newsome DA, Fibach E, Yoshida M, Su MS. Induction of gammaglobin by histone deacetylase inhibitors. Blood 90(5), 2075-2083 (1997).
68. Cao H, Stamatoyannopoulos G. Histone deacetylase inhibitor FK228 is a potent inducer of human fetal hemoglobin. Am. J. Hematol. 81(12), 981-983 (2006).
69. Cao H, Stamatoyannopoulos G, Jung M. Induction of human gamma globin gene expression by histone deacetylase inhibitors. Blood 103(2), 701-709 (2004).
70. Perrine SP, Castaneda SA, Boosalis MS, White GL, Jones BM, Bohacek R. Induction of fetal globin in betathalassemia: Cellular obstacles and molecular progress. Ann. NY Acad. Sci. 1054, 257-265 (2005).
71. Mankidy R, Faller DV, Mabaera R et al. Short-chain fatty acids induce gammaglobin gene expression by displacement of a HDAC3-NCoR repressor complex. Blood 108(9), 3179-3186 (2006).
72. Muralidhar SA, Ramakrishnan V, Kalra IS, Li W, Pace BS. Histone deacetylase 9 activates gamma-globin gene expression in primary erythroid cells. J. Biol. Chem. 286(3), 2343-2353 (2011).
73. Johnson J, Hunter R, McElveen R, Qian XH, Baliga BS, Pace BS. Fetal hemoglobin induction by the histone deacetylase inhibitor, scriptaid. Cell. Mol. Biol. (Noisy-le-grand) 51(2), 229-238 (2005).
74. Denslow SA, Wade PA. The human Mi-2/NuRD complex and gene regulation. Oncogene 26(37), 5433-5438 (2007).
75. Lettre G, Sankaran VG, Bezerra MA et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc. Natl Acad. Sci. USA 105(33), 11869-11874 (2008).
76. Uda M, Galanello R, Sanna S et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc. Natl Acad. Sci. USA 105(5), 1620-1625 (2008).
77. Sankaran VG, Menne TF, Xu J et al. Human fetal hemoglobin expression is regulated by the developmental stagespecific repressor BCL11A. Science 322(5909), 1839-1842 (2008).
78. Hsiao CH, Li W, Lou TF, Baliga BS, Pace BS. Fetal hemoglobin induction by histone deacetylase inhibitors involves generation of reactive oxygen species. Exp. Hematol. 34(3), 264-273 (2006).
79. Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res. 15(1), 11-18 (2005).
80. Collins AF, Dover GJ, Luban NL. Increased fetal hemoglobin production in patients receiving valproic acid for epilepsy. Blood 84(5), 1690-1691 (1994).
81. Selby R, Nisbet-Brown E, Basran RK, Chang L, Olivieri NF. Valproic acid and augmentation of fetal hemoglobin in individuals with and without sickle cell disease. Blood 90(2), 891-893 (1997).
82. Dover GJ, Brusilow S, Samid D. Increased fetal hemoglobin in patients receiving sodium 4-phenylbutyrate. N. Engl. J. Med. 327(8), 569-570 (1992).
83. Collins AF, Pearson HA, Giardina P, McDonagh KT, Brusilow SW, Dover GJ. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: A clinical trial. Blood 85(1), 43-49 (1995).
84. Johnstone RW. Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer. Nat. Rev. Drug Discov. 1(4), 287-299 (2002).
85. Fathallah H, Weinberg RS, Galperin Y, Sutton M, Atweh GF. Role of epigenetic modifications in normal globin gene regulation and butyrate-mediated induction of fetal hemoglobin. Blood 110(9), 3391-3397 (2007).
86. Xu J, Sankaran VG, Ni M et al. Transcriptional silencing of {gamma}-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev. 24(8), 783-798 (2010).
87. Zhou D, Liu K, Sun CW, Pawlik KM, Townes TM. KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching. Nat. Genet. 42(9), 742-744 (2010).
88. Xu J, Peng C, Sankaran VG et al. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334(6058), 993-996 (2011).