{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:55:35Z","timestamp":1788612935408,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T00:00:00Z","timestamp":1394150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Induction of fetal haemoglobin (<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>b<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>) is a promising therapeutic approach for the treatment of \u03b2\u2010thalassaemia and sickle cell disease (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>). Several pharmacological agents, such as hydroxycarbamide (<jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>) and butyrates, have been shown to induce the \u03b3\u2010globin genes (<jats:styled-content style=\"fixed-case\">HBG<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">HBG<\/jats:styled-content>2). However, their therapeutic use is limited due to weak efficacy and an inhibitory effect on erythroid differentiation. Thus, more effective agents are needed. The histone deacetylase (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) inhibitors are potential therapeutic haemoglobin (<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>b) inducers able to modulate gene expression through pleiotropic mechanisms. We investigated the effects of a <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> inhibitor, Givinostat (<jats:styled-content style=\"fixed-case\">GVS<\/jats:styled-content>), on erythropoiesis and haemoglobin synthesis and compared it with sodium butyrate and HC. We used an <jats:italic>in vitro<\/jats:italic> erythropoiesis model derived from peripheral <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34<jats:sup>+<\/jats:sup> cells of healthy volunteers and <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> donors. <jats:styled-content style=\"fixed-case\">GVS<\/jats:styled-content> effects on erythroid proliferation and differentiation and on <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>b synthesis were investigated. We found that <jats:styled-content style=\"fixed-case\">GVS<\/jats:styled-content> at high concentrations delayed erythroid differentiation with no specific effect on <jats:styled-content style=\"fixed-case\">HBG<\/jats:styled-content>1\/2 transcription. At a low concentration (1\u00a0nmol\/l), GVS induced Hb production with no effects on cells proliferation and differentiation. The efficacy of <jats:styled-content style=\"fixed-case\">GVS<\/jats:styled-content> 1\u00a0mol\/l in <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>b induction <jats:italic>in vitro<\/jats:italic> was comparable to that of <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content> and butyrate. Our results support the evaluation of <jats:styled-content style=\"fixed-case\">GVS<\/jats:styled-content> as a new candidate molecule for the treatment of the haemoglobinophathies due to its positive effects on haemoglobin production at low and non\u2010toxic concentrations.<\/jats:p>","DOI":"10.1111\/bjh.12814","type":"journal-article","created":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T13:17:35Z","timestamp":1394198255000},"page":"714-721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Modulation of gamma globin genes expression by histone deacetylase inhibitors: an <i>in vitro<\/i> study"],"prefix":"10.1111","volume":"165","author":[{"given":"Luisa","family":"Ronzoni","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico University of Milan Milan Italy"},{"name":"UO Genetica Medica Fondazione IRCCS 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