{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:43:18Z","timestamp":1785163398971,"version":"3.55.0"},"posted":{"date-parts":[[2023,6,9]]},"group-title":"Cancer Biology","reference-count":37,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Treatment of relapsed\/refractory B cell acute lymphoblastic leukemia (B-ALL) remains a challenge, particularly in patients who do not respond to traditional chemotherapy or immunotherapy. The objective of this study was to assess the efficacy of fedratinib, a semi selective JAK2 inhibitor and venetoclax, a selective BCL-2 inhibitor, on human B-ALL using both single-agent and combinatorial treatments. The combination treatment of fedratinib and venetoclax improved killing of the human B-ALL cell lines RS4;11 and SUPB-15 in vitro over single-agent treatments. This combinatorial effect was not detected in the human B-ALL cell line NALM-6, which was less responsive to fedratinib due to the absence of Flt3 expression. The combination treatment induces a unique gene expression profile relative to single-agent treatment and with an enrichment in apoptotic pathways. Finally, the combination treatment was superior to single agent treatment in an in vivo xenograft model of human B-ALL, with a two-week treatment regimen significantly improving overall survival while inducing CD19 expression. Overall, our data demonstrates the efficacy of a combinatorial treatment strategy of fedratinib and venetoclax against human B-ALL expressing high levels of Flt3.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of Implication<\/jats:title>\n                  <jats:p>The combination treatment of fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression and has the potential to be a salvage therapy for patients with relapsed\/refractory B-ALL.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.06.07.544058","type":"posted-content","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T23:50:14Z","timestamp":1686354614000},"source":"Crossref","is-referenced-by-count":3,"title":["Combination fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression"],"prefix":"10.64898","author":[{"given":"Sean 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