Role of Genomic Biomarkers in Increasing Fetal Hemoglobin Levels Upon Hydroxyurea Therapy and in β-Thalassemia Intermedia: A Validation Cohort Study

References

• Wahed A, Dasgupta A. Hematology and Coagulation: A Comprehensive Review for Board Preparation, Certification and Clinical Practice, 1st ed. Amsterdam (NL): Elsevier; 2015.
   Google Scholar
• Origa R. β-Thalassemia. Genet Med. 2017;19(6):609–619.
   PubMed Web of Science ®Google Scholar
• Iarovaia OV, Kovina AP, Petrova NV, et al. Genetic and epigenetic mechanisms of β-globin gene switching. Biochemistry (Mosc). 2018;83(4):381–392.
   PubMed Web of Science ®Google Scholar
• Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013;3(1):a011643.
   PubMed Web of Science ®Google Scholar
• Amid A, Saliba AN, Taher AT, et al. Thalassaemia in children: from quality of care to quality of life. Arch Dis Child. 2015;100(11):1051–1057.
   PubMed Web of Science ®Google Scholar
• Taher A, Vichinsky E, Musallam K, et al. Guidelines for the management of non transfusion dependent thalassaemia (NTDT). [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Available at http://www.ncbi.nlm.nih.gov/books/NBK190453/.
   Google Scholar
• Porter J, Viprakasit V, Kattamis A. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT), 3rd ed. [Internet] Nicosia (Cyprus): Thalassaemia International Federation; 2014. Chapter 3, Iron overload and chelation. Available at https://www.ncbi.nlm.nih.gov/books/NBK269373/.
   Google Scholar
• Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the Optimal Care study. Blood. 2010;115(10):1886–1892.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Porter JB, Viprakasit V, et al. A paradigm shift on β-thalassaemia treatment: how will we manage this old disease with new therapies? Blood Rev. 2018;32(4):300–311.
   PubMed Web of Science ®Google Scholar
• Baronciani D, Angelucci E, Potschger U, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant. 2016;51(4):536–541.
   PubMed Web of Science ®Google Scholar
• Pule GD, Mowla S, Novitzky N, et al. A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease. Expert Rev Hematol. 2015;8(5):669–679.
   PubMed Web of Science ®Google Scholar
• Weatherall DJ. Towards molecular medicine: reminiscences of the haemoglobin field, 1960–2000. Br J Haematol. 2001;115(4):729–738.
   PubMed Web of Science ®Google Scholar
• Cokic VP, Andric SA, Stojilkovic SS, et al. Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells. Blood. 2008;111(3):1117–1123.
   PubMed Web of Science ®Google Scholar
• Park JI, Choi HS, Jeong JS, et al. Involvement of p38 kinase in hydroxyurea-induced differentiation of K562 Cells. Cell Growth Differ. 2001;12(9):481–486.
   PubMedGoogle Scholar
• Pourfarzad F, Von Lindern M, Azarkeivan A, et al. Hydroxyurea responsiveness in β-thalassemic patients is determined by the stress response adaptation of erythroid progenitors and their differentiation propensity. Haematologica. 2013;98(5):696–704.
   PubMed Web of Science ®Google Scholar
• Lohani N, Bhargava N, Munshi A, et al. Pharmacological and molecular approaches for the treatment of β hemoglobin disorders. J Cell Physiol. 2018;233(6):4563–4577.
   PubMed Web of Science ®Google Scholar
• Gravia A, Chondrou V, Kolliopoulou A, et al. Correlation of SIN3A genomic variants with β-hemoglobinopathies disease severity and hydroxyurea treatment efficacy. Pharmacogenomics. 2016;17(16):1785–1793.
   PubMed Web of Science ®Google Scholar
• Wyszynski DF, Baldwin CT, Cleves MA, et al. Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. Cell Mol Biol (Noisy-le-grand). 2004;50(1):23–33.
   PubMed Web of Science ®Google Scholar
• Thein SL, Menzel S, Peng X, et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc Natl Acad Sci USA. 2007;104(27):11346–11351.
   PubMed Web of Science ®Google Scholar
• Sebastiani P, Wang L, Nolan VG, et al. Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations. Am J Hematol. 2008;83(3):189–195.
   PubMed Web of Science ®Google Scholar
• Banan M, Bayat H, Azarkeivan A, et al. The XmnI and BCL11A single nucleotide polymorphisms may help predict hydroxyurea response in Iranian β-thalassemia patients. Hemoglobin. 2012;36(4):371–380.
   PubMed Web of Science ®Google Scholar
• Kumkhaek C, Taylor JG, Zhu J, et al. Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia. Br J Haematol. 2008;141(2), 254–259.
   PubMed Web of Science ®Google Scholar
• Steinberg MH, Lu ZH, Barton FB, et al. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood. 1997;89(3):1078–1088.
   PubMed Web of Science ®Google Scholar
• Yavarian M, Karimi M, Bakker E, et al. Response to hydroxyurea treatment in Iranian transfusion-dependent β-thalassemia patients. Haematologica. 2004;89(10):1172–1178.
   PubMed Web of Science ®Google Scholar
• Alebouyeh M, Moussavi F, Haddad-Deylami H, et al. Hydroxyurea in the treatment of major β-thalassemia and importance of genetic screening. Ann Hematol. 2004;83(7):430–433.
   PubMed Web of Science ®Google Scholar
• Dixit A, Chatterjee TC, Mishra P, et al. Hydroxyurea in thalassemia intermedia – a promising therapy. Ann Hematol. 2005;84(7):441–446.
   PubMed Web of Science ®Google Scholar
• Patrinos GP, Grosveld FG. Pharmacogenomics and therapeutics of hemoglobinopathies. Hemoglobin. 2008;32(1-2):229–236.
   PubMed Web of Science ®Google Scholar
• Nagel RL, Fabry ME. Sickle cell anemia as a multigenetic disease: new insights into the mechanism of painful crisis. Prog Clin Biol Res. 1984;165:93–102.
   PubMedGoogle Scholar
• Lettre G, Sankaran VG, Bezerra MAC, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and β-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA. 2008;105(33):11869–11874.
   PubMed Web of Science ®Google Scholar
• Ma Q, Wyszynski DF, Farrell JJ, et al. Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea. Pharmacogenomics. 2007;7(6):386–394.
   Web of Science ®Google Scholar
• Tafrali C, Paizi A, Borg J, et al. Genomic variation in the MAP3K5 gene is associated with β-thalassemia disease severity and hydroxyurea treatment efficacy. Pharmacogenomics. 2013;14(5):469–483.
   PubMed Web of Science ®Google Scholar
• 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 β-hemoglobinopathy patients. Pharmacogenomics. 2012;13(13):1487–1500.
   PubMed Web of Science ®Google Scholar
• Gravia A, Chondrou V, Sgourou A, et al. Individualizing fetal hemoglobin augmenting therapy for β-type hemoglobinopathies patients. Pharmacogenomics. 2014;15(10):1355–1364.
   PubMed Web of Science ®Google Scholar
• Chalikiopoulou C, Tavianatou AG, Sgourou A, et al. Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients. Pharmacogenomics. 2016;17(4):393–403.
   PubMed Web of Science ®Google Scholar
• Asadov C, Alimirzoeva Z, Mammadova T, et al. β-Thalassemia intermedia: a comprehensive overview and novel approaches. Int J Hematol. 2018;108(1):5–21.
   PubMed Web of Science ®Google Scholar
• Galanello R, Melis MA, Ruggeri R, et al. β0 Thalassemia trait in Sardinia. Hemoglobin. 1979;3(1):33–46.
   PubMed Web of Science ®Google Scholar
• Papachatzopoulou A, Kourakli A, Makropoulou P, et al. Genotypic heterogeneity and correlation to intergenic haplotype within high Hb F β-thalassemia intermedia. Eur J Haematol. 2006;76(4):322–330.
   PubMed Web of Science ®Google Scholar
• Desmet F-O, Hamroun D, Lalande M, et al. Human splicing finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 2009;37(9):e67–e67.
   PubMed Web of Science ®Google Scholar
• RD Connect (http://rd-connect.eu).
   Google Scholar
• MicroSNiPer (http://epicenter.ie-freiburg.mpg.de).
   Google Scholar
• Barenboim M, Zoltick BJ, Guo Y, et al. MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targets. Hum Mutat. 2010;31(11):1223–1232.
   PubMed Web of Science ®Google Scholar
• Papachatzopoulou A, Kaimakis P, Pourfarzad F, et al. Increased γ-globin gene expression in β-thalassemia intermedia patients correlates with a mutation in 3 HS1. Am J Hematol. 2007;82(11):1005–1009.
   PubMed Web of Science ®Google Scholar
• Giannopoulou E, Bartsakoulia M, Tafrali C, et al. A single nucleotide polymorphism in the HBBP1 gene in the human β-globin locus is associated with a mild β-thalassemia disease phenotype. Hemoglobin. 2012;36(5):433–445.
   PubMed Web of Science ®Google Scholar
• Chondrou V, Kolovos P, Sgourou A, et al. Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients. Hum Genom. 2017;11(1):24.
   PubMedGoogle Scholar
• Patrinos GP, Antonarakis SE. Human hemoglobin. In: Speicher M, Antonarakis SE, Motulsky AG, Editors. Vogel and Motulsky’s Human Genetics, 4th ed. Heidelberg (Germany): Springer. 2010:365–401.
   Google Scholar
• Akinsheye I, Alsultan A, Solovieff N, et al. Fetal hemoglobin in sickle cell anemia. Blood. 2011;118(1):19–27.
   PubMed Web of Science ®Google Scholar
• Ikuta T, Ausenda S, Cappellini MD. Mechanism for fetal globin gene expression: role of the soluble guanylate cyclase-cGMP-dependent protein kinase pathway. Proc Natl Acad Sci USA. 2001;98(4):1847–1852.
   PubMed Web of Science ®Google Scholar
• Bloch KD, Wolfram JR, Brown DM, et al. Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17. Genomics. 1995;27(3):526–530.
   PubMed Web of Science ®Google Scholar