{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:32:14Z","timestamp":1791595934843,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL164583\u201001"],"award-info":[{"award-number":["1R01HL164583\u201001"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Hydroxycarbamide (HC) is the most widely used therapeutic for individuals with sickle cell disease (SCD, including sickle cell anemia and other forms of the disease). HC's clinical benefits are primarily associated with its ability to induce foetal haemoglobin (HbF); this limited view of HC's therapeutic potential may lead to its discontinuation when a modest amount of HbF is induced. A better understanding of the HbF\u2010independent effects of HC on genes and pathways relevant to SCD pathophysiology is therefore needed. In this study, we performed bulk RNA\u2010Seq on whole blood samples collected from a cohort of 25 paediatric patients with SCD to identify genes and pathways that are affected by treatment with HC. At the maximum tolerated dose (MTD) of HC, patients showed altered expression levels of several genes and biological pathways. Pathways related to haeme metabolism, interferon\u2010alpha response, and interferon\u2010gamma response were significantly downregulated at HC MTD relative to the matched pre\u2010HC samples. Pathways linked with IL2\u2010STAT5 signalling and TNF\u03b1 signalling via NF\u2010K\u03b2 were observed to be up\u2010regulated at HC MTD. These results illustrate the range of effects exerted by HC during therapy for SCD and pave the way for an improved understanding of the HbF induction\u2010independent benefits of HC.<\/jats:p>","DOI":"10.1111\/bjh.19839","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T07:56:03Z","timestamp":1731916563000},"page":"713-720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of hydroxycarbamide treatment on the whole\u2010blood transcriptome in sickle cell disease"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1462-1591","authenticated-orcid":false,"given":"Varsha","family":"Bhat","sequence":"first","affiliation":[{"name":"Center for Integrative Genomics School of Biological Sciences, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alka A.","family":"Potdar","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Karen","family":"Yu","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Gibson","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics School of Biological Sciences, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2837-2255","authenticated-orcid":false,"given":"Vivien A.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Data & statistics on sickle cell disease. CDC [Internet] [cited 2023 Apr 4]. Available from:https:\/\/www.cdc.gov\/ncbddd\/sicklecell\/data.html"},{"key":"e_1_2_12_3_1","unstructured":"Adopting consensus text general assembly urges member states United Nations system to raise awareness of sickle\u2013cell anaemia on 19 June each year. UN Press [Internet] [Cited 2023 Apr 4]. 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