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Transl. Med."],"published-print":{"date-parts":[[2026,6,24]]},"abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is an aggressive leukemia with high rates of chemoresistance and relapse. Patients with AML undergoing induction chemotherapy often have delayed erythropoietic recovery and febrile neutropenia. Infection is a leading cause of mortality in this population. There is an unmet need to improve disease-specific outcomes in patients with AML undergoing cytotoxic chemotherapy. AML, at diagnosis, is characterized by increased levels of circulating iron due to erythroid block and cell death, which is further aggravated upon intensive chemotherapy. We hypothesized that iron, particularly toxic non\u2013transferrin-bound iron (NTBI), can be redistributed away from AML cells and bacteria into nonmalignant transferrin receptor (CD71)\u2013expressing cells by administering exogenous iron-free apotransferrin (apoTF). Using mouse models of AML, we show that mice treated with human apoTF had decreased NTBI and increased bone marrow erythropoiesis and B cell responses. ApoTF treatment resulted in normalization of bone marrow blood vessels and reduction of lipid peroxidation in endothelial cells. Crucially, apoTF combined with chemotherapy resulted in a reduction of AML cells and in improved survival, which was dependent on adaptive immunity. We established a murine model of\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    sepsis in leukemic mice receiving chemotherapy. We show that apoTF administration increased the survival of\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    \u2013infected mice. Mechanistically, apoTF treatment decreased the levels of circulating C-C motif chemokine ligand 2 (CCL2) and interleukin-6 through reduced expression of CCL2 in lipopolysaccharide-polarized macrophages. Our results demonstrate an overall benefit of iron redistribution induced by transferrin in combination with cytotoxic chemotherapy in AML.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu0167","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:58:11Z","timestamp":1782323891000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Transferrin in combination with induction chemotherapy improves outcomes in mouse models of acute myeloid leukemia"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-4844","authenticated-orcid":true,"given":"Marta","family":"Lopes","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3471-0153","authenticated-orcid":true,"given":"Filipa","family":"Lemos","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal."},{"name":"Immunethep, Biocant Park, 3060-197 Cantanhede, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-2386","authenticated-orcid":true,"given":"L\u00eddia","family":"Rocha","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3765-6667","authenticated-orcid":true,"given":"Carolina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4484-9922","authenticated-orcid":true,"given":"Catarina","family":"Moreira-Barbosa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-4891","authenticated-orcid":true,"given":"Joana P.","family":"Reis","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-4580","authenticated-orcid":true,"given":"Tiago L.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-7714","authenticated-orcid":true,"given":"Andr\u00e9 M. 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