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• W4380201863 abstract "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. Overall, our data demonstrates the efficacy of a combinatorial treatment strategy of fedratinib and venetoclax against human B-ALL expressing high levels of Flt3.Combination fedratinib and venetoclax reduces the survival and proliferation of FLT3 + B-ALL in vitro. Gene set enrichment analysis of RNA from B-ALL treated with fedratinib and venetoclax identified dysregulation of pathways associated with apoptosis, DNA repair and proliferation.Combination fedratinib and venetoclax reduces the number of peripheral blood B-ALL blasts in vivo, improving overall survival while also increasing CD19 expression." @default.
• W4380201863 created "2023-06-11" @default.
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• W4380201863 date "2023-06-09" @default.
• W4380201863 modified "2023-09-23" @default.
• W4380201863 title "Combinatorial fedratinib and venetoclax treatment is effective on human B cell acute lymphoblastic leukemia with high Flt3 expression" @default.
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• W4380201863 doi "https://doi.org/10.1101/2023.06.07.544058" @default.
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