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In certain patients with myelodysplastic syndrome, DFX can also provide a dramatic therapeutic benefit, improving red blood cell production and decreasing transfusion requirements. Nuclear Factor\u2010kappa B (NF\u2010kB) signalling has been implicated as a potential mechanism behind this phenomenon, with studies focusing on the effect of DFX on haematopoietic progenitors. Here, we examine the phenotypic and transcriptional effects of DFX throughout myeloid cell maturation in both murine and human model systems. The effect of DFX depends on the stage of differentiation, with effects on mitochondrial reactive oxygen species (ROS) production and NF\u2010kB pathway regulation that vary between progenitors and neutrophils. DFX triggers a greater increase in mitochondrial ROS production in neutrophils and this phenomenon is mitigated when cells are cultured in hypoxic conditions. Single\u2010cell transcriptomic profiling revealed that DFX decreases the expression of NF\u2010kB and MYC (c\u2010Myc) targets in progenitors and decreases the expression of PU.1 (SPI1) gene targets in neutrophils. Together, these data suggest a role of DFX in impairing terminal maturation of band neutrophils.<\/jats:p>","DOI":"10.1111\/bjh.19782","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T01:29:57Z","timestamp":1727400597000},"page":"2000-2007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deferasirox, an iron chelator, impacts myeloid differentiation by modulating <scp>NF<\/scp>\u2010<scp>kB<\/scp> activity via mitochondrial <scp>ROS<\/scp>"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7904-4747","authenticated-orcid":false,"given":"Nathan E.","family":"Jeffries","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sadreyev","sequence":"additional","affiliation":[{"name":"Center 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