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We demonstrate that activation of the histamine H\n                    <jats:sub>2<\/jats:sub>\n                    receptor by its specific agonist, amthamine, enhances GR transcriptional activity induced by dexamethasone in both artificial promoter\u2010driven luciferase reporter assays and endogenous GR\u2010responsive genes. Mechanistically, histamine H\n                    <jats:sub>2<\/jats:sub>\n                    receptor signaling exerts a dual regulatory effect: an inhibitory influence mediated by cAMP and a stimulatory effect through inhibition of the PI3K\u2010AKT\u2013mTOR\u2010S6K pathway and activation of the ERK pathway. Furthermore, while dexamethasone reduces leukemic cell proliferation at high doses, it increases it at lower concentrations, an effect that is abrogated by amthamine. Moreover, the combination of the glucocorticoid and the H\n                    <jats:sub>2<\/jats:sub>\n                    agonist reestablishes leukemic cell sensitivity to cytarabine, thereby restoring its cytotoxicity. Together, these findings offer insight into the molecular mechanisms and therapeutic potential of the interplay between histamine H\n                    <jats:sub>2<\/jats:sub>\n                    ligands and GR agonists, and may help guide dosage optimization and mitigate the well\u2010known side effects of glucocorticoid therapy, with potential clinical implications for the treatment of acute myeloid leukemia.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70314","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:12:56Z","timestamp":1789445576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross\u2010Talk Between Histamine\n                    <scp>\n                      H\n                      <sub>2<\/sub>\n                    <\/scp>\n                    Receptor and Glucocorticoid Receptor: Potential Implications in Acute Myeloid Leukemia Treatment"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6186-2835","authenticated-orcid":false,"given":"Valeria","family":"Torralba\u2010Agu","sequence":"first","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA) Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-6471","authenticated-orcid":false,"given":"Natalia","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA) Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Shayo","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda y Farmacolog\u00eda Molecular, Instituto de Biolog\u00eda y Medicina Experimental CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Davio","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA) Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-577X","authenticated-orcid":false,"given":"C. 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