{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:28:37Z","timestamp":1793312917132,"version":"4.5.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Donor cell leukaemia (DCL) is a complication of haematopoietic stem cell transplantation where donated cells become malignant within the patient\u2019s bone marrow. As DCL predominates as acute myeloid leukaemia, we hypothesized that the cytokine storm following chemotherapy played a role in promoting and supporting leukaemogenesis. Cytokines have also been implicated in genotoxicity; thus, we explored a cell line model of the human bone marrow (BM) to secrete myeloid cytokines following drug treatment and their potential to induce micronuclei. HS-5 human stromal cells were exposed to mitoxantrone (MTX) and chlorambucil (CHL) and, for the first time, were profiled for 80 cytokines using an array. Fifty-four cytokines were detected in untreated cells, of which 24 were upregulated and 10 were downregulated by both drugs. FGF-7 was the lowest cytokine to be detected in both untreated and treated cells. Eleven cytokines not detected at baseline were detected following drug exposure. TNF\u03b1, IL6, GM-CSF, G-CSF, and TGF\u03b21 were selected for micronuclei induction. TK6 cells were exposed to these cytokines in isolation and in paired combinations. Only TNF\u03b1 and TGF\u03b21 induced micronuclei at healthy concentrations, but all five cytokines induced micronuclei at storm levels, which was further increased when combined in pairs. Of particular concern was that some combinations induced micronuclei at levels above the mitomycin C positive control; however, most combinations were less than the sum of micronuclei induced following exposure to each cytokine in isolation. These data infer a possible role for cytokines through chemotherapy-induced cytokine storm, in the instigation and support of leukaemogenesis in the BM, and implicate the need to evaluate individuals for variability in cytokine secretion as a potential risk factor for complications such as DCL.<\/jats:p>","DOI":"10.1093\/mutage\/gead018","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T15:23:36Z","timestamp":1686929016000},"page":"201-215","source":"Crossref","is-referenced-by-count":5,"title":["Genotoxicity of cytokines at chemotherapy-induced \u2018storm\u2019 concentrations in a model of the human bone marrow"],"prefix":"10.1093","volume":"38","author":[{"given":"Harshini S H","family":"Asurappulige","sequence":"first","affiliation":[{"name":"School of Applied Sciences, University of the West of England , Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D","family":"Thomas","sequence":"additional","affiliation":[{"name":"School of Applied Sciences, University of the West of England , Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Ruth","family":"Morse","sequence":"additional","affiliation":[{"name":"School of Applied Sciences, University of the West of England , Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"2023082413193310300_CIT0001","author":"Cancer Research UK (CRUK)","year":"2022"},{"key":"2023082413193310300_CIT0002","first-page":"39","article-title":"Novel therapeutic options in acute myeloid leukemia","volume":"6","author":"Medinger","year":"2016","journal-title":"Leuk Res 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