{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:16:43Z","timestamp":1770967003577,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4939,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1993,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5\u2010azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating \u03b3\u2010chain synthesis. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830420118","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T12:51:28Z","timestamp":1172062288000},"page":"91-95","source":"Crossref","is-referenced-by-count":12,"title":["Fetal hemoglobin reactivation in baboon and man: A short perspective"],"prefix":"10.1002","volume":"42","author":[{"given":"Donald","family":"Lavelle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Desimone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Heller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198801143180207"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1978.tb05813.x"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1182\/blood.V67.5.1404.1404","article-title":"High fetal hemoglobin production in sickle cell anemia in the eastern province of Saudi Arabia is genetically determined","volume":"67","author":"Miller BA","year":"1986","journal-title":"Blood"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1182\/blood.V62.2.370.370","article-title":"5\u2010azacytidine increases \u03b3\u2010globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia","volume":"62","author":"Ley TJ","year":"1983","journal-title":"Blood"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1182\/blood.V69.1.109.109","article-title":"Hydroxyurea induced augmentation of fetal hemoglobin production patients with sickle cell anemia","volume":"69","author":"Charache S","year":"1987","journal-title":"Blood"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.43.020192.002433"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/313320a0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.7005"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.12.6420"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.7.2923"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198404053101401"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111464"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.3.735.735"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199004123221504"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6200940"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.14.4428"},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1182\/blood.V67.4.1083.1083","article-title":"On the mechanism of HbF elevations in the baboon by erythropoietic stress and pharmacologic manipulation","volume":"67","author":"Lavelle D","year":"1986","journal-title":"Blood"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6254144"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198212093072401"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1989.tb07734.x"},{"key":"e_1_2_1_22_2","unstructured":"LowreyC NienhuisAW: Pharmacologic manipulation of globin gene expression with 5\u2010azacytidine has produced long\u2010term therapeutic benefits in two patients with beta\u2010thalassemia.Blood(Suppl)368a 1991."},{"key":"e_1_2_1_23_2","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1182\/blood.V64.5.1053.1053","article-title":"Production of F cells in sickle cell anemia: Regulation by a genetic locus or loci separate from the \u03b2\u2010globin cluster","volume":"64","author":"Boyer SH","year":"1984","journal-title":"Blood"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109654"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1981.tb07213.x"},{"key":"e_1_2_1_26_2","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1182\/blood.V63.5.1088.1088","article-title":"Speciation in the baboon and its relation to \u03b3\u2010chain heterogeneity and to the response to induction of HbF by 5\u2010azacytidine","volume":"63","author":"DeSimone J","year":"1984","journal-title":"Blood"},{"key":"e_1_2_1_27_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1182\/blood.V60.2.519.519","article-title":"Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress","volume":"60","author":"DeSimone J","year":"1982","journal-title":"Blood"},{"key":"e_1_2_1_28_2","first-page":"73","article-title":"Differences in burst morphology among baboon species","volume":"17","author":"Eves E","year":"1986","journal-title":"Exp Hematol"},{"key":"e_1_2_1_29_2","first-page":"261","volume-title":"Hemoglobin Switching, Part A: Transcriptional Regulation","author":"Lavelle D","year":"1989"},{"key":"e_1_2_1_30_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1182\/blood.V77.1.174.174","article-title":"Variations in the hemoglobin F production among normal and sickle cell adults is not related to nucleotide substitutions in the gamma promoter regions","volume":"77","author":"Economou EP","year":"1991","journal-title":"Blood"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(81)90476-9"},{"key":"e_1_2_1_32_2","first-page":"862","article-title":"Fetal hemoglobin synthesis in baboons (Papio cynocephalus)","volume":"91","author":"DeSimone J","year":"1978","journal-title":"J Lab Clin Med"},{"key":"e_1_2_1_33_2","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1016\/S0021-9258(18)32839-4","article-title":"Changes in the \u03b3\u2010chain heterogeneity of hemoglobin F of the baboon (Papio cynocephalus) postnatally and after partial switching to hemoglobin F production by various stimuli","volume":"258","author":"Schroeder WA","year":"1983","journal-title":"J Biol Chem"},{"key":"e_1_2_1_34_2","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1182\/blood.V54.5.1176.1176","article-title":"Hemopoietic stress and fetal hemoglobin synthesis: Comparative studies in vivo and in vitro","volume":"54","author":"DeSimone J","year":"1979","journal-title":"Blood"},{"key":"e_1_2_1_35_2","first-page":"919","article-title":"Studies of HbF in adult nonanemic baboons: HbF expression in erythroid colonies decreases as the level of maturation of erythroid progenitors advances","volume":"13","author":"de Torrealba RA","year":"1985","journal-title":"Exp Hematol"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198708133170704"},{"key":"e_1_2_1_37_2","first-page":"286A","article-title":"Hydroxyurea therapy in sickle cell disease: Effects of dose schedule and recombinant erythropoietin on hematological and rheological properties","volume":"76","author":"Rodgers GP","year":"1990","journal-title":"Blood"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90280-R"},{"key":"e_1_2_1_39_2","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1182\/blood.V79.7.1861.1861","article-title":"Influence of Steel factor on hemoglobin synthesis in sickle cell disease","volume":"79","author":"Miller BA","year":"1992","journal-title":"Blood"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198502073120602"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.22.8540"},{"key":"e_1_2_1_42_2","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1182\/blood.V72.6.1961.1961","article-title":"\u03b1\u2010amino\u2010N\u2010butyric acid stimulates fetal hemoglobin in the adult","volume":"72","author":"Constantoulakis P","year":"1988","journal-title":"Blood"},{"key":"e_1_2_1_43_2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1182\/blood.V74.1.454.454","article-title":"Sodium butyrate enhances fetal globin gene expression in erythroid cells of patients with HbSS and \u03b2 thalassemia","volume":"74","author":"Perrine SP","year":"1989","journal-title":"Blood"},{"key":"e_1_2_1_44_2","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1182\/blood.V74.6.1963.1963","article-title":"On the induction of fetal hemoglobin by butyrates: In vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5\u2010AzaC and AraC","volume":"74","author":"Constantoulakis P","year":"1989","journal-title":"Blood"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.13.3954"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.9.4690"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90133-Y"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.20.120186.001051"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6348"},{"key":"e_1_2_1_50_2","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1182\/blood.V78.9.2248.2248","article-title":"Erythroid\u2010restricted expression of homeobox genes of the HOX2 locus","volume":"78","author":"Mathews CHE","year":"1991","journal-title":"Blood"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7318"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.14.3843"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/349257a0"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/341033a0"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.2830420118","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.2830420118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T07:17:38Z","timestamp":1698218258000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.2830420118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1993,1]]}},"alternative-id":["10.1002\/ajh.2830420118"],"URL":"https:\/\/doi.org\/10.1002\/ajh.2830420118","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1]]}}}