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Here, we found that inhibitors of epigenetic modifiers, including VPA, TSA, and 5\u2010Aza\u20102'\u2010deoxycytidine, can induce phenotypic transformation from Jurkat cells into B\u2010cell\u2010like cells. When Jurkat cells were treated with 5\u2010Aza combined with VPA, B cell and stem cell marker expression was observed. These gene expression pattern changes were most remarkable in the optimized B cell induction conditions provided by the cocultured and genetically modified murine bone marrow OP9 cells. In such conditions, Jurkat cells were endowed with the ability to secrete B cell cytokines, and B lymphocyte\u2010related genes and pathways were activated. In studying the mechanism underlying Jurkat cell reprogramming by 5\u2010Aza and VPA, we found that PAX5, the key transcription factor regulating B cell development, was significantly upregulated. Treatment with 5\u2010Aza and VPA inhibited the methylation of CpG islands and upregulated the acetylated H3K9 modification in the PAX5 promoter region, respectively, thus epigenetically activating the expression of PAX5 and promoting the reprogramming of Jurkat cells. Similar reprogramming results were also observed in primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells following treatment with 5\u2010Aza and VPA. Our results provide a de novo paradigm for the reprogramming of T cells through epigenetic modifications.\n                  <\/jats:p>","DOI":"10.1002\/btpr.70023","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T06:51:31Z","timestamp":1742194291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["5\u2010Aza combined with\n                    <scp>VPA<\/scp>\n                    reprograms human T lineage acute leukemia Jurkat cells into B\u2010cell\u2010like cells by epigenetic activation of\n                    <scp>PAX5<\/scp>"],"prefix":"10.1002","volume":"41","author":[{"given":"Wenjin","family":"Xi","sequence":"first","affiliation":[{"name":"State key laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Immunology Fourth Military Medical University  Xi'an 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