Recent trends for novel options in experimental biological therapy of β-thalassemia

Expert Opinion on Biological Therapy

Volumn 14, Issue 10, 2014, Pages 1443-1454

  Finotti, Alessia ^a,b   Gambari, Roberto ^a,b  

^a UNIVERSITY OF FERRARA   (Italy)

^b Associazione Veneta per la Lotta Alla Talassemia   (Italy)

Author keywords

Fetal hemoglobin induction; Gene therapy; Induced pluripotent cells; MicroRNA; Thalassemia; Transcription factors

Indexed keywords

GAMMA GLOBIN ZINC FINGER; GLOBIN MESSENGER RNA; HEMOGLOBIN ALPHA CHAIN; HEMOGLOBIN F; HEMOGLOBIN GAMMA CHAIN; HYDROXYUREA; MICRORNA; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR NUCLEASE; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; HEMOGLOBIN BETA CHAIN;

BETA THALASSEMIA; BIOLOGICAL ACTIVITY; BIOLOGICAL THERAPY; CELL DIFFERENTIATION; ERYTHROID CELL; ERYTHROID PRECURSOR CELL; GENE ACTIVATION; GENE EXPRESSION; GENE INDUCTION; GENE SILENCING; GENE TARGETING; GENE THERAPY; GLOBIN GENE; HOMOLOGOUS RECOMBINATION; HUMAN; NONHUMAN; PROMOTER REGION; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; BETA-THALASSEMIA; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; PHYSIOLOGY; PROCEDURES;

BETA-GLOBINS; BETA-THALASSEMIA; BIOLOGICAL THERAPY; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; GENETIC THERAPY; HUMANS;

EID: 84907051216     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1517/14712598.2014.927434     Document Type: Review

References (130)

1. Giardine B, Borg J, Viennas E, et al. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res 2014;42(Database issue):D1063-9
2. Patrinos GP, Kollia P, Papadakis MN. Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies. Hum Mutat 2005;26:399-412
3. Old JM. Screening and genetic diagnosis of haemoglobin disorders. Blood Rev 2003;17:43-53
4. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010;5:11
5. Colah R, Gorakshakar A, Nadkarni A. Global burden, distribution and prevention of beta-thalassemias and hemoglobin E disorders. Expert Rev Hematol 2010;3:103-17
6. Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet 2001;2:245-55
7. Weatherall DJ. Pathophysiology of thalassaemia. Baillieres Clin Haematol 1998;11:127-46
8. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012;379:373-83
9. Quek L, Thein SL. Mole cular therapies in beta-thalassaemia. Br J Haematol 2007;136:353-65
10. Lederer CW, Basak AN, Aydinok Y, et al. An electronic infrastructure for research and treatment of the thalassemias and oth er hemoglobinopathies: the Euromediterranean ITHANET project. Hemoglobin 2009;33:163-76
11. Gambari R,Fibach E, Medicinal chemistry of fetal hemoglobin inducers for treatment of beta-thalassemia, Curr Med Chem, 2007, 14, 199-212.
12. Testa U. Fetal hemoglobin chemical inducers for treatment of hemoglobinopathies. Ann Hematol 2009;88:505-28
13. Olivieri NF, Britte nham GM. Management of the thalassemias. Cold Spring Harb Perspect Med 2013;3:a011767
14. Goss C, Giardina P, Degtyaryova D, et al. Red blood cell transfusions for thalassemia: results of a survey assessing current practice and proposal of evidence-based guidelines. Transfusion 2014. [Epub ahead of print]
15. Poggiali E, Cassinerio E, Zanaboni L, Cappellini MD. An update on iron chelation therapy. Blood Transfus 2012;10:411-22
16. Cunningham MJ. Update on thalassemia: clinical care and complications. Pediatr Clin North Am 2008;55:447-60
17. Michlitsch JG, Walters MC. Recent advances in bone marrow transplantation in hemoglobinopathies. Curr Mol Med 2008;8:675-89
18. de Witte T. The role of iron in patients after bone marrow transplantation. Blood Rev 2008;22:S22-8
19. Gambari R. Alternative options for DNA-based experimental therapy of beta-thalassemia. Expert Opin Biol Ther 2012;12:443-62
20. Bianchi N, Zuccato C, Lampronti I, et al. Fetal hemoglobin inducers from the natural world: a novel approach for identification of drugs for the treatment of {beta}-thalassemia and sickle-cell anemia. Evid Based Co mplement Alternat Med 2009;6:141-51
21. Porteus MH. Mammalian gene targeting with designed zinc finger nucleases. Mol Ther 2006;13:438-46
22. Zou J, Mali P, Hua ng X, et al. Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 2011;118:4599-608
23. Katada H, Komiyama M. Artif icial restriction DNA cutters to promote homologous recombination in human cells. Curr Gene Ther 2011;11:38-45
24. Lin Y, Cradick TJ, Bao G. Designing and testing the activities of TAL effector nucleases. Methods Mol Biol 2014;1114:203-19
25. Sun N, Zhao H. Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs. Biotechnol Bioeng 2014;111:1048-53
26. Voit RA, Hendel A, Pruett-Miller SM, Porteus MH. Nuclease-mediated gene editing by homologous recombination of the human globin locus. Nucleic Acids Res 2014;42:1365-78
27. Hockemeyer D, Soldner F, Beard C, et al. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 2009;27:851-7
28. Perez EE, Wang J, Miller JC, et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 2008;26:808-16
29. Urnov FD, Miller JC, Lee YL, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 2005;435:646-51
30. Voit RA, McMahon MA, Sawyer SL, Porteus MH. Generation of an HIV resistant T-cell line by targeted ''stacking'' of restriction factors. Mol Ther 2013;21:786-95
31. Hockemeyer D, Wang H, Kiani S, et al. Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 2011;29:731-4
32. Miller JC,Tan S,Qiao G,et al, A TALE nuclease architecture for efficient genome editing, Nat Biotechnol, 2010, 29, 143-8.
33. Reyon D, Tsai SQ, Khayter C, et al. FLASH assembly of TALENs for highthroughput genome editing. Nat Biotechnol 2012;30:460-5
34. Mussolino C, Morbitzer R, Lutge F, et al. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res 2011;39:9283-93
35. Ma N , Liao B, Zhang H, et al. Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free betathalassemiainduced pluripotent stem cells. J Biol Chem 2013;288:34671-9
36. Wang Y, Zheng CG, Jiang Y, et al. Genetic correction of beta-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice. Cell Res 2012;22:637-48
37. Sebastiano V, Maeder ML, Angstman JF, et al. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells 2011;29:171 7-26
38. Wilber A, Hargrove PW, Kim YS, et al. Therapeutic levels of fetal hemoglobin in erythroid progeny of beta-thalassemic CD34+ cells after lentiviral vectormediated gene transfer. Blood 2011;117: 2817-26
39. Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 2010;467:318-22
40. Kaiser J. Gene therapy. Beta-thalassemia treatment succeeds, with a caveat. Science 2009;326:1468-9
41. Dong A, Rivella S, Breda L. Gene therapy for hemoglobinopathies: progress and challenges. Transl Res 2013;161:293-306
42. Boulad F, Rivière I, Sadelain M. Gene therapy for homozygous beta-thalassemia. Is it a reality? Hemoglobin 2009;33:S188-96
43. Bank A. Hemoglobin gene therapy for beta-thalassemia. Hematol Oncol Clin North Am 2010;24:1187-201
44. Yannaki E, Emery DW, Stamatoyannopoulos G. Gene therapy for beta-thalassaemia: the continuing challenge. Expert Rev Mol Med 2010;12:e31
45. Yannaki E, Papayannopoulou T, Jonlin E, et al. Hematopoietic stem cell mobilization for gene therapy of adult patients with severe beta-thalassemia: re sults of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects. Mol Ther 2012;20:230-8
46. Boulad F, Wang X, Qu J, et al. Safe mobilization of CD34+ cells in adults with beta-thalassemia and validation of effective globin gene transfer for clinical investigation. Blood 2014;123:1483-6
47. Ye L, Chang JC, Lin C, et al. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proc Natl Acad Sci USA 2009;106:9826-30
48. Tubsuwan A, Abed S, Deichmann A, et al. Parallel assessment of globin lentiviral transfer in induced pluripotent stem cells and adult hematopoietic stem cells derived from the same transplanted beta-thalassemia patient. Stem Cells 2013;31:1785-94
49. Chandrakasan S, Malik P. Gene therapy for hemoglobinopathies: the state of the field and the future. Hematol Oncol Clin North Am 2014;28:199-216 50.
50. Persons DA, Hargrove PW, Allay ER, et al. The degree of phenotypic correction of murine beta-thalassemia intermedia following lentiviral-mediated transfer of a human gamma-globin gene is influenced by chromosomal positi on effects and vector copy number. Blood 2003;101:2175-83
51. Hanawa H, Hargrove PW, Kepes S, et al. Extended beta-globin locus control region elements promote consistent therapeutic expression o f a gamma-globin lentiviral vector in murine beta-thalassemia. Blood 2004;104:2281-90
52. Nishino T, Tubb J, Emery DW. Partial correction of murine beta-thalassemia with a gammaretrovirus vector for human gamma-globin. Blood Cells Mol Dis 2006;37:1-7.
53. Nishino T,Cao H,Stamatoyannopoulos G,Emery DW, Effects of human gamma-globin in murine beta-thalassaemia, Br J Haematol, 2006;134, 100-8.
54. Zuccato C, Breda L, Salvatori F, et al. A combined approach for betathalassemia based on gene therapymediated adult hemoglobin (HbA) production and fetal hemoglobin (HbF) induction. Ann H ematol 2012;91:1201-13
55. Breda L, Rivella S, Zuccato C, Gambari R. Combining gene therapy and fetal hemoglobin induction for treatment of beta-thalassemia. Expert Rev Hematol 2013;6:255-64
56. Kafri T. Lentivirus vectors: difficulties and hopes before clinical trials. Curr Opin Mol Ther 2001;3:316-26
57. Persons DA. The challenge of obtaining therapeutic levels of genetically modified hematopoietic stem cells in betathalassemia patients. Ann NY Acad Sci 2010;1202:69-74
58. Negre O, Fusil F, Colomb C, et al. Correction of murine beta-thalassem ia after minimal lentiviral gene transfer and homeostatic in vivo erythroid expansion. Blood 2011;117:5321-31
59. Voon HP, Vadolas J. Controlling alphaglobin: a review of alpha-globin expression and its impact on beta-thalassemia. Haematologica 2008;93:1868-76
60. Voon HP, Wardan H, Vadolas J. siRNA-mediated reduction of alphaglobin results in phenotypic improvements in beta-thalassemic cells. Haematologica 2008;93:1238-42
61. Xie SY, Ren ZR, Zhang JZ, et al. Restoration of the balanced alpha/betaglobin gene expression in beta654-thalassemia mice using combined RNAi and antisense RNA approach. Hum Mol Genet 2007;16:2616-25
62. Voon HP, Wardan H, Vadolas J. Co-inheritance of alpha-and betathalassaemia in mice ameliorates thalassaemic phenotype. Blood Cells Mol Dis 2007;39:184-8
63. Mast KJ, Hammond S , Qualman SJ, Kahwash SB. The coinheritance of betaand alpha-thalassemia: a review of one patient and her family. Lab Hematol 2009;15:30-3
64. Ronzoni L, Sonzogni L, Fossati G, et al. Modulation of gamma globin genes expression by histone deacetylase Inhibitors: an in vitro study. Br J Haematol 2014;165(5):714-21
65. Reid ME, El Beshlawy A, Inati A, et al. A double-blind, p lacebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease. Am J Hematol 2014. [Epub ahead of print]
66. Perrine SP, Pace BS, Faller DV. Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies. Hematol Oncol Clin North Am 2014;28:233-48
67. Ahmadvand M, Noruzinia M, Fard AD, et al. The role o f epigenetics in the induction of fetal hemoglobin: a combination therapy approach. Int J Hematol Oncol Stem Cell Res 2014;8:9-14
68. Fard AD, Hosseini SA, Shahjahani M, et al. Evaluation of nov el fetal hemoglobin inducer drugs in treatment of beta-hemoglobinopathy disorders. Int J Hematol Oncol Stem Cell Res 2013;7:47-54
69. Rahim F, Allahmoradi H, Salari F, et al. Evaluation of signa ling pathways involved in gamma-globin gene induction using fetal hemoglobininducer drugs. Int J Hematol Oncol Stem Cell Res 2013;7:41-6
70. Qian X, Chen J, Zhao D, et al. Plastrum testudinis in duces gamma-globin gene expression through epigenetic histone modifications within the gamma-globin gene promoter via activation of the p38 MAPK signaling pathway. Int J Mol Med 2013;31:1418-28
71. Santos Franco S, De Falco L, Ghaffari S, et al. Resveratrol accelerates erythroid maturation by activation of FOXO3 and ameliorates anemia in beta-thalassemic mice. Haematologica 2014;99:267-75
72. Ma YN, Chen MT, Wu ZK, et al. Emodin can induce K562 cells to erythroid differentiation and improve the expression of globin genes. Mol Cell Biochem 2013;382:127-36
73. Italia K, Jijina F, Mercha nt R, et al. Comparison of in-vitro and in-vivo response to fetal hemoglobin production and gamma-mRNA expression by hydroxyurea in hemoglobinopathies. Indian J Hum Genet 2013;19:251-8
74. Pecoraro A, Rigano P, Troia A, et al. Quantification of HBG mRNA in primary erythroid cultures: prediction of the response to hydroxyurea in sickle cell and beta-thalassemia. Eur J Haematol 2014;92:66-72.
75. Voskaridou E,Kalotychou V,Loukopoulos D, Clinical and laboratory effects of long-term administration of hydroxyurea to patients with sickle-cell/beta-thalassaemia, Br J Haematol, 1995, 89, 479-84.
76. Rigano P, Rodgers GP, Renda D, et al. Clinical and hematological responses to hydroxyurea in sicilian patients with Hb S/beta-thalassemia. Hemoglobin 2001;25:9-17
77. Zimmerma n SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 2004;103:2039-45
78. Hankins JS, Ware RE, Rogers ZR, et al. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood 2005;106:2269-75
79. Ji Q, Fischer AL, Brown CR, et al. Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367. Nucleic Acids Res 2014;42:6158-67
80. Barrow JJ, Li Y, Hossain M, et al. Dissecting t he function of the adult beta-globin downstream promoter region using an artificial zinc finger DNAbinding domain. Nucleic Acids Res 2014;42(7):4363-74
81. Onori A, Pisani C, Strimpakos G, et al. Utr oUp is a novel six zinc finger artificial transcription factor that recognises 18 base pairs of the utrophin promoter and efficiently drives utrophin upregulation. BMC Mol Biol 2013;14:3
82. Reyon D, Maeder ML, Khayter C, et al. Engineering customized TALE nucleases (TALENs) and TALE transcription factors by fast ligation-based automatable solid-phase high-throughput (FLASH) assembly. Curr Protoc Mol Biol 2013;Chapter 12:Unit 12.16
83. Uhde-Stone C, Gor N, Chin T, et al. A do-it-yourself protocol for simple transcription activator-like effector assembly. Biol Proced Online 2013;15:3
84. Hu J, Lei Y, Wong WK, et al. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. Nucl Acids Res 2014;42:4375-90
85. Grä slund T, Li X, Magnenat L, et al. Exploring strategies for the design of artificial transcription factors: targeting sites proximal to known regulatory regions for the induction of gammaglobin expression and the treatment of sickle cell disease. J Biol Chem 2005;280:3707-14
86. Wilber A, Tschulena U, Hargrove PW, et al. A zinc-finger transcriptional activator designed to interact with the gamma-globin gene promoters enhances fetal hemoglobin production in primary human adult erythroblasts. Blood 2010;115:3033-41
87. Costa FC, Fedosyuk H, Neades R, et al. Induction of fetal hemoglobin in vivo mediated by a synthetic gamma-globin zinc finger activator. Anemia 2012;2012:507894
88. Viprakasit V, Ekwattanakit S, Riolueang S, et al. Mutations in Kruppel-like factor 1 cause transfusiondependent hemolytic anemia and persistence of embryonic globin gene expression. Blood 2014;123:1586-95
89. Roosjen M, McColl B, Kao B, et al. Transcriptional regulators Myb and BCL11A interplay with DNA methyltransferase 1 in developmental silencing of embryonic and fetal beta-like globin genes. FASEB J 2014;28:1610-20
90. Thein SL, Menzel S. Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol 2009;145:455-67
91. Forget BG. Progress in understanding the hemoglobin switch. N Engl J Med 2011;365:852-4
92. Sankaran VG, Xu J, Byron R, et al. A functional element necessary for fetal hemoglobin silencing. N Engl J Med 2011;365:807-14
93. Zhou D, Liu K, Sun CW, et al. KLF1 regulates BCL11A expression and gamma-to beta-globin gene switching. Nat Genet 2010;42:742-4
94. Sankaran VG, Menne TF, Xu J, et al. Human fetal hemoglobin expression is regulated by the developmental stagespecific repressor BCL11A. Science 2008;322:1839-42
95. Tanabe O, McP hee D, Kobayashi S, et al. Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2and TR4. EMBO J 2007;26:2295-306
96. Tanabe O,Shen Y,Liu Q,et al, The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription, Genes Dev, 2007, 21, 2832-44.
97. Cui S, Kolodziej KE, Obara N, et al. Nuclear receptors TR2 and TR4 recruit multiple epigenetic tr anscriptional corepressors that associate specifically with the embryonic beta-type globin promoters in differentiated adult erythroid cells. Mol Cell Biol 2011;31:3298-311
98. Campbell AD, Cui S, Shi L, et al. Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. Proc Natl Acad Sci USA 2011;108:18808-13
99. Xu XS, Hong X, Wang G. Induction of endogenous gamma-globin gene expression with decoy oligonucleotide targeting Oct-1 transcription factor consensus sequence. J Hematol Oncol 2009;2:15-26
100. Jiang J, Best S, Menzel S, et al. cMYB is involved in the regulation of fetal hemoglobin production in adults. Blood 2006;108:1077-83
101. Sankaran VG, Xu J, Orkin SH. Transcriptional silencing of fetal hemoglobin by BCL11A. Ann NY Acad Sci 2010;1202:64-8
102. Sankaran VG. Targeted therapeutic strategies for fetal hemoglobin induction. Hematology Am Soc Hematol Educ Program 2011;2011:459-65
103. Borg J, Papadopoulos P, Georgitsi M, et al. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet 2010;42:801-5.
104. Borg J, Phylactides M, Bartsakoulia M, et al. KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in beta-hemoglobinopathy patients. Pharmacogenomics 2012;13:1487-500
105. Stadhouders R, Aktuna S, Thongjuea S, et al. HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. J Clin Invest 2014;124:1699-710
106. Amaya M, Desai M, Gnanapragasam MN, et al. Mi2beta-mediated silencing of the fetal gamma-globin gene in adult erythroid cells. Blood 2013;121:3493-501
107. Thie l KW, Giangrande PH. Therapeutic applications of DNA and RNA aptamers. Oligonucleotides 2009;19:209-22
108. Borgatti M, Finotti A, Romanelli A, et al. Peptide nucleic acids (PNA)-DNA chi meras targeting transcription factors as a tool to modify gene expression. Curr Drug Targets 2004;5:735-44
109. Bauer DE, Kamran SC, Lessard S, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 2013;342:253-7
110. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2010;5:522-31
111. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11:597-610
112. Sontheimer EJ, Carthew RW . Silence from within: endogenous siRNAs and miRNAs. Cell 2005;122:9-12
113. Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development 2005;132:4653-62
114. Fu YF, Du TT, Dong M, et al. Mir-144 selectively regulates embryonic alpha-hemoglobin synthesis during primitive erythropoiesis. Blood 2009;113:1340-9
115. . Bianchi N, Zuccato C, Lampronti I, et al. Expression of miR-210 during erythroid differentiation and induction of gamma-globingene expression. BMB Rep 2009;42:493-9
116. Sarakul O, Vatt anaviboon P, Tanaka Y, et al. Enhanced erythroid cell differentiation in hypoxic condition is in part contributed by miR-210. Blood Cells Mol Dis 2013;51:98-103
117. Fabbri E,Manicardi A,Tedeschi T,et al, Modulation of the biological activity of microRNA-210 with peptide nucleic acids (PNAs), ChemMedChem, 2011, 6, 2192-202.
118. Kouhkan F, Soleimani M, Daliri M, et al. miR-451 up-regulation, induce erythroid differentiation of CD133+cells independent of cytokine cocktails. Iran J Basic Med Sci 2013;16:756-63
119. Yuan JY, Wang F, Yu J, et al. MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells. J Cell Mol Med 2009;13:4551-9
120. Noh SJ, Miller SH, Lee YT, et al. Let-7 microRNAs are developmentally regulated in circulating human erythroid cells. J Transl Med 2009;7:98
121. Svasti S, Masaki S, Penglong T, et al. Expression of microRNA-451 in normal and thalassemic erythropoiesis. Ann Hematol 2010;89:953-8
122. Sturgeon CM, Chicha L, Ditadi A, et al. Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1+ cells. Dev Cell 2012;23:45-57
123. Bianchi N, Zuccato C, Finotti A, et al. Involvement of miRNA in erythroid differentiation. Epigenomics 2012;4:51-65
124. Sankaran VG, Menne TF, Şćepanović D, et al. MicroRNA-15a and-16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci USA 2001;108:1519-24
125. Gabbianelli M, Testa U, Morsilli O, et al. Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex. Haematologica 2010;95:1253-60
126. Azzouzi I, Moest H, Winkler J, et al. MicroRNA-96 directly inhibits gammaglobin expression in human erythropoiesis. PLoS One 2011;6:e22838
127. Lulli V, Romania P, Morsilli O, et al. MicroRNA-486-3p regulates gammaglobin expression in human erythroid cells by directly modulating BCL11A. PLoS One 2013;8:e60436
128. Lee YT, de Vasconcellos JF, Yuan J, et al. LIN28B-mediated expression of fetal h emoglobin and production of fetallike erythrocytes from adult human erythroblasts ex vivo. Blood 2013;122:1034-41
129. Ma Y, Wang B, Jiang F, et al. A feedback loop consisting of microRNA 23a/27 a and the beta-like globin suppressors KLF3 and SP1 regulates globin gene expression. Mol Cell Biol 2013;33:3994-4007
130. Alijani S, Alizadeh S, Kazemi A, et al. Evaluation of the effect of miR -26b upregulation on HbF expression in erythroleukemic K-562 cell line. Avicenna J Med Biotechnol 2014;6:53-6