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Expert Review of Precision Medicine and Drug Development
Personalized medicine in drug development and clinical practice
Volume 4, 2019 - Issue 6
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Review

Sickle cell disease in the era of precision medicine: looking to the future

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Pages 357-367 | Received 05 Sep 2019, Accepted 31 Oct 2019, Published online: 07 Nov 2019

References

  • Garner C, Tatu T, Reittie JE, et al. Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood. 2000;95(1):342–346.
  • Dover GJ, Boyer SH, Charache S, et al. Individual variation in the production and survival of F cells in sickle-cell disease. N Engl J Med. 1978;299(26):1428–1435.
  • Ngo DA, Aygun B, Akinsheye I, et al. Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin. Br J Haematol. 2012;156(2):259–264.
  • Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007;21(1):37–47.
  • Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750–760.
  • Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;8(12):1383–1389.
  • 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.
  • Bao EL, Lareau CA, Brugnara C, et al. Heritability of fetal hemoglobin, white cell count, and other clinical traits from a sickle cell disease family cohort. Am J Hematol. 2019;94(5):522–527.
  • Gibney GT, Panhuysen CIM, So JCC, et al. Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong. Am J Hematol. 2008;83(6):458–464.
  • Powars DR. Beta S-gene-cluster haplotypes in sickle cell anemia. Clinical and hematologic features. Hematol Oncol Clin North Am. 1991;5(3):475–493.
  • Powars DR. Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure. Semin Hematol. 1991;28(3):202–208.
  • Powars D, Hiti A. Sickle cell anemia. Beta s gene cluster haplotypes as genetic markers for severe disease expression. Am J Dis Child. 1960;1993(147):1197–1202.
  • Perrine RP, Pembrey ME, John P, et al. Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects. Ann Int Med. 1978;88(1):1–6.
  • Perrine RP, Brown MJ, Clegg JB, et al. Benign sickle-cell anæmia. Lancet. 1972;300(7788):1163–1167.
  • Vathipadiekal V, Alsultan A, Baltrusaitis K, et al. Homozygosity for a haplotype in the HBG2-OR51B4 region is exclusive to Arab-Indian haplotype sickle cell anemia. Am J Hematol. 2016;91(6):E308–311.
  • Vathipadiekal V, Farrell JJ, Wang S, et al. A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia. Am J Hematol. 2016;91(11):1118–1122.
  • Al-Ali ZA, Fallatah RK, Aljaffer EA, et al. ANTXR1 intronic variants are associated with fetal hemoglobin in the Arab-Indian haplotype of sickle cell disease. Acta Haematol. 2018;140(1):55–59.
  • Nagel RL, Fabry ME, Pagnier J, et al. Hematologically and genetically distinct forms of sickle cell anemia in Africa. The senegal type and the Benin type. N Engl J Med. 1985;312(14):880–884.
  • Shaikho EM, Farrell JJ, Chui DHK, et al. Cis- and trans-acting expression quantitative trait loci differentially regulate gamma-globin gene expression. bioRxiv. 2018 Apr 20. DOI:10.1101/304899.
  • Masuda T, Wang X, Maeda M, et al. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science. 2016;351(6270):285–289.
  • Martyn GE, Wienert B, Yang L, et al. Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding. Nat Genet. 2018;50(4):498–503.
  • Liu N, Hargreaves VV, Zhu Q, et al. Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch. Cell. 2018;173(2):430–442.
  • Galarneau G, Palmer CD, Sankaran VG, et al. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat Genet. 2010;42(12):1049–1051.
  • 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.
  • Menzel S, Garner C, Gut I, et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet. 2007;39(10):1197–1199.
  • Craig JE, Rochette J, Fisher CA, et al. Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach. Nat Genet. 1996;12(1):58–64.
  • Farrell JJ, Sherva RM, Chen Z-Y, et al. A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression. Blood. 2011;117(18):4935–4945.
  • 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(4):1699–1710.
  • Canver MC, Lessard S, Pinello L, et al. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci. Nat Genet. 2017;49(4):625–634.
  • Morrison TA, Wilcox I, Luo H-Y, et al. A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression. Blood Cells Mol Dis. 2018;69:1–9.
  • Vinjamur DS, Bauer DE, Orkin SH. Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies. Br J Haematol. 2018;180(5):630–643.
  • Lettre G, Sankaran VG, Bezerra MAC, 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. 2008;105(33):11869–11874.
  • 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. 2008;105(5):1620–1625.
  • Bauer DE, Kamran SC, Lessard S, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science. 2013;342(6155):253–257.
  • Canver MC, Smith EC, Sher F, et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015;527(7577):192–197.
  • Steinberg MH, Chui DHK, Dover GJ, et al. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014;123(4):481–485.
  • Milton JN, Gordeuk VR, Taylor JG, et al. Prediction of fetal hemoglobin in sickle cell anemia using an ensemble of genetic risk prediction models. Circ Cardiovasc Genet. 2014;7(2):110–115.
  • Gardner K, Fulford T, Silver N, et al. g(HbF): a genetic model of fetal hemoglobin in sickle cell disease. Blood Adv. 2018;2(3):235–239.
  • Steinberg MH, Embury SH. Alpha-thalassemia in blacks: genetic and clinical aspects and interactions with the sickle hemoglobin gene. Blood. 1986;68(5):985–990.
  • Taylor JG, Nolan VG, Mendelsohn L, et al. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One. 2008;3(5):e2095.
  • Belfer I, Youngblood V, Darbari DS, et al. A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia. Am J Hematol. 2014;89(2):187–193.
  • Jhun EH, Sadhu N, Yao Y, et al. Glucocorticoid receptor single nucleotide polymorphisms are associated with acute crisis pain in sickle cell disease. Pharmacogenomics. 2018;19(13):1003–1011.
  • Sebastiani P, Ramoni MF, Nolan V, et al. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet. 2005;37(4):435–440.
  • Flanagan JM, Frohlich DM, Howard TA, et al. Genetic predictors for stroke in children with sickle cell anemia. Blood. 2011;117(24):6681–6684.
  • Taylor JG, Tang DC, Savage SA, et al. Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood. 2002;100(13):4303–4309.
  • Hoppe C. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103(6):2391–2396.
  • Zahr R, Lebensburger J, Rampersaud E, et al. Children with sickle cell anemia and APOL1 genetic variants develop albuminuria early in life. Haematologica. 2019;104(9):e385–e387.
  • Steinberg MH. Clinical variability in sickle cell anemia. 2019. UpToDate. Walters Kluwer, Waltham, MA.
  • Ilboudo Y, Bartolucci P, Rivera A, et al. Genome-wide association study of erythrocyte density in sickle cell disease patients. Blood Cells Mol Dis. 2017;65:60–65.
  • Ma S, Cahalan S, LaMonte G, et al. Common PIEZO1 allele in African populations causes RBC dehydration and attenuates Plasmodium infection. Cell. 2018;173(443–455):e12.
  • Rooks H, Brewin J, Gardner K, et al. A gain of function variant in PIEZO1 (E756del) and sickle cell disease. Haematologica. 2019;104(3):e91–e93.
  • Milton JN, Rooks H, Drasar E, et al. Genetic determinants of haemolysis in sickle cell anaemia. Br J Haematol. 2013;161(2):270–278.
  • Raffield LM, Ulirsch JC, Naik RP, et al. Common α-globin variants modify hematologic and other clinical phenotypes in sickle cell trait and disease. PLoS Genet. 2018;14(3):e1007293.
  • Milton JN, Shaikho EM, Steinberg MH. Haemolysis in sickle cell anaemia: effects of polymorphisms in α-globin gene regulatory elements. Br J Haematol. 2019;186(2):363–364.
  • Conran N, Belcher JD. 2018; Inflammation in sickle cell disease. Clin Hemorheol Microcirc. 2018;68(2–3):263–299.
  • Sebastiani P, Nolan VG, Baldwin CT, et al. A network model to predict the risk of death in sickle cell disease. Blood. 2007;110(7):2727–2735.
  • Belini Junior E, Silva DGH, de Torres LS, et al. Severity of Brazilian sickle cell disease patients: severity scores and feasibility of the Bayesian network model use. Blood Cells Mol Dis. 2015;54(4):321–327.
  • Desai AA, Lei Z, Bahroos N, et al. Association of circulating transcriptomic profiles with mortality in sickle cell disease. Blood. 2017;129(22):3009–3016.
  • Du M, Van Ness S, Gordeuk V, et al. Biomarker signatures of sickle cell disease severity. Blood Cells Mol Dis. 2018;72:1–9.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–676.
  • Takahashi K, Yamanaka SA. developmental framework for induced pluripotency. Development. 2015;142(19):3274–3285.
  • Deshmukh RS, Kovács KA, Dinnyés A. Drug discovery models and toxicity testing using embryonic and induced pluripotent stem-cell-derived cardiac and neuronal cells. Stem Cells Int. 2012;2012:379569.
  • Chun YS, Byun K, Lee B. Induced pluripotent stem cells and personalized medicine: current progress and future perspectives. Anat Cell Biol. 2011 Dec;44(4):245–255. .
  • Park S, Gianotti-Sommer A, Molina-Estevez FJ, et al. A comprehensive, ethnically diverse library of sickle cell disease-specific induced pluripotent stem cells. Stem Cell Rep. 2017;8(4):1076–1085.
  • Vanuytsel K, Matte T, Leung A, et al. Induced pluripotent stem cell-based mapping of β- globin expression throughout human erythropoietic development. Blood Adv. 2018;2(15):1998–2011.
  • Leung A, Zulick E, Skvir N, et al. Notch and aryl hydrocarbon receptor signaling impact definitive hematopoiesis from human pluripotent stem cells. Stem Cells. 2018;36(7):1004–1019.
  • Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004;3(8):711–715.
  • McGann PT, Niss O, Dong M, et al. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019;94(8):871–879.
  • Quinn CT. l-Glutamine for sickle cell anemia: more questions than answers. Blood. 2018;132(7):689–693.
  • Niihara Y, Miller ST, Kanter J, et al. Investigators of the phase 3 trial of l-glutamine in sickle cell disease.; a phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018 Jul 19;379(3):226–235.
  • Vichinsky E, Hoppe CC, Ataga KI, et al. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381(6):509–519.
  • Wood JC. Brain O2 reserve in sickle cell disease. Blood. 2019;133(22):2356–2358.
  • Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429–439.
  • Orkin SH, Bauer DE. Emerging genetic therapy for sickle cell disease. Annu Rev Med. 2019;70(1):257–271.
  • Romero Z, DeWitt M, Walters MC. Promise of gene therapy to treat sickle cell disease. Expert Opin Biol Ther. 2018;18(11):1123–1136.
  • Joseph JJ, Abraham AA, Fitzhugh CD. When there is no match, the game is not over: alternative donor options for hematopoietic stem cell transplantation in sickle cell disease. Semin Hematol. 2018;55(2):94–101.
  • Leonard A, Tisdale JF. Stem cell transplantation in sickle cell disease: therapeutic potential and challenges faced. Expert Rev Hematol. 2018;11(7):547–565.

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