Articles

The Role of Epigenetics in the Induction of Fetal Hemoglobin: A Combination Therapy Approach

Abstract

Background: β-thalassemia considers worldwide public health disorders. Novel fetal hemoglobin inducer agents such as thalidomide and sodium butyrate have been attended for ameliorating clinical complications of such disorders.
Material and Methods:
We used thalidomide and sodium butyrate for increasing the level of fetal hemoglobin in erythroid progenitors. Briefly, after isolation of CD133+ stem cells from umbilical cord blood and differentiation into erythroid lineage, erythroid progenitors were treated with thalidomide and sodium butyraye as single and combination. H3K4 histone methylation was evaluated following fetal hemoglobin induction using chromatin immuno percipitation (ChIP) technique.
Results: The results of this study showed that the effect of thalidomide on increasing of H3K4 methylation was highest compared to sodium butyrate and combination of both agents (p < 0.05).
Conclusion:
Consequently, our study of the epigenetic modification of the γ-globin suggests that histone H3K4 dimethylation are significant for the regulation of developmental stage-specific expression of the γ-globin genes.

Saki N, Dehghanifard A, Kaviani S, Jalali far M, Mousavi H, Al-Ali K, Rahim F. Beta thalassemia: Epidemiology, diagnostic and treatment approach in Iran. Genetics in the 3rd millennium 2012; 10[1]:2674-83.

Farshdousti Hagh M, Dehghani Fard A, Saki N, Shahjahani M, Kaviani S. Molecular Mechanisms of hemoglobin F induction. IJHOSCR. 2011;5(4):5-9.

Rahim F, Kaikhaei B, Zandian K, Hoseini A. Co-inheritance of alpha-and beta-thalassemia in Khuzestan Province, Iran. Hematology 2008; 13[1]:59-64.

Steinberg MH, Rodgers GP. Pharmacologic modulation of fetal hemoglobin. Medicine [Baltimore]. 2001 Sep;80[5]:328-44

Gambari R, Fibach E. Medicinal chemistry of fetal hemoglobin inducers for treatment of beta-thalassemia. Curr Med Chem. 2007; 14[2]:199-212.

Wood WG, Weatherall DJ, Clegg JB. Interaction of hetrocellular hereditary persistence of fetal hemoglobin with beta thalassemia and sickle anemia. Nature. 1976; 264[5583]:247-9.

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al.Effect of hydroxyureaon the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.N Engl J Med. 1995; 332[20]:1317-22.

Dehghani Fard A, Kaviani S, Saki N, Mortaz E. The emerging role of immunomodulatory agents in fetal hemoglobin induction. IJHOSCR. 2012;6(4):35-36.

Atweh GF, Sutton M, Nassif I, Boosalis V, Dover GJ, Wallenstein S, et al. Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease.Blood 1999 15; 93[6]:1790-7.

Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999 Jul 1;163[1]:380-6.

Corral LG, Muller GW, Moreira AL, Chen Y, Wu M, Stirling D, Kaplan G.Selection of novel analogs of thalidomide with enhanced tumor necrosis factor alpha inhibitory activity. Mol Med. 1996 Jul; 2[4]:506-15.

Masera N, Tavecchia L, Capra M, Cazzaniga G, Vimercati C, PozziL,et al. Optimal response to thalidomide in a patient with thalassaemia major resistant to conventional therapy. Blood Transfus. 2010; 8[1]:63-5.

Lenz W, Knapp K. Thalidomide embryopathy. Arch Environ Health. Arch Environ Health. 1962; 5:100-5.

Eriksson T, Bjorkman S, Hoglund P. Clinical pharmacology of thalidomide. Eur J ClinPharmacol. 2001; 57[5]:365-76.

Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS Jr. Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem. 2001; 276[25]:22382-7.

Stephens TD, Fillmore BJ. Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology. Teratology. 2000; 61[3]:189-95.

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, et al. Anti-tumor activity of thalidomide in refractory multiple myeloma. 222N Engl J Med. 1999;341[21]:1565-71.

Raza A, Meyer P, Dutt D, Zorat F, Lisak L, Nascimben F, et al. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood. 2001; 98[4]:958-65.

Davie JR. Inhibition of histone deacetylase activity by butyrate. 22%[J Nutr. 2003;133[7]:2485-93.

Fathallah H, Weinberg RS, Galperin Y, Sutton M, AtwehGF. Role of epigenetic modification in normal gene regulation and butyrate-mediated induction of fetal hemoglobin. Blood. 2007; 110[9]:3391-7.

Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006; 125[2]:315-26.

Mankidy R, Faller DV, Mabaera R, Lowrey CH, Boosalis MS, White GL, et al. Short chain fatty acids induce gamma-globin gene expression by displacement of a HDAC3-NCoR repressor complex. Blood. 2006; 108[9]:3179-86.

Dehghani Fard A, Kaviani S, Noruzinia M, Soleimani M, Abroun S, Hajifathali, et al. Synergistic effect of sodium butyrate and thalidomide in the induction of fetal hemoglobin expression in erythroid progenitors derived from cord blood CD133 + cells. Zahedan J Res Med Sci (ZJRMS) 2012; 14(7): 29-33.

Dehghani Fard A, Kaviani S, Noruzinia M, Soleimani M, Abroun S, Chegeni R, et al. Evaluation of H3 histone methylation and colony formation in erythroid progenitors treated with thalidomide and sodium butyrate. Laboratory Hematology. 2013; 19[1]:41-5.

Aerbajinai W, Zhu J, Gao Z, Chin K, Rodgers GP. Thalidomide induces globin gene expression through increased reactive oxygen species–mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis. Blood. 2007; 110[8]:2864-71.

Collins AF, Pearson HA, Giardina P, McDonagh KT, Brusilow SW, Dover GJ. Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. Blood. 1995; 1; 85[1]:43-9.

Im H, Grass JA, Christensen HM, Perkins A, Bresnick EH. Histone deacetylase-dependent establishment and maintenance of broad low-level histone acetylation within a tissue-specific chromatin domain. Biochemistry. 2002 41(51):15152-60.

Hsiao CH, Li W, Lou TF, Baliga BS, Pace BS. Fetal hemoglobin induction by histone deacetylase inhibitors involves generation of reactive oxygen species. ExpHematol. 2006; 34[3]:264-73.

Ahmadvand M, Noruzinia M, Soleimani M, Kaviani S, Abroun S, Dehghanifard A, Mahmoodinia Meymand M. In vitro inducion on of gamma globin gene in erythroid cells derived from CD133+ by thalidomide and sodium butyrate. Genetics in the 3rd millennium. 2011;9(2): 2373-8.

Dehghani Fard A, Kaviani S, Noruzinia M, Saki N, Mortaz E. Epigenetic modulation on fetal hemoglobin induction. IJHOSCR. 2012; 6(1): 11-12.

Files
IssueVol 8, No 1 (2014) QRcode
SectionArticles
Keywords
Sodium butyrate Thalidomide β-thalassemia γ-globin

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ahmadvand M, Noruzinia M, Fard AD, Zohour MM, Tabatabaiefar MA, Soleimani M, Kaviani S, Abroun S, Beiranvand S, Saki N. The Role of Epigenetics in the Induction of Fetal Hemoglobin: A Combination Therapy Approach. Int J Hematol Oncol Stem Cell Res. 1;8(1):9-14.