{"doi":"10.1101/2023.06.07.544058","title":"Combination fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression","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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396657,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1172428,"name":"Haley C Bell","orcid":null,"position":1,"is_corresponding":false},{"id":338812,"name":"Nicholas J Hess","orcid":"0000-0001-5720-9305","position":2,"is_corresponding":false},{"id":309493,"name":"Nguyet-Minh Hoang","orcid":null,"position":3,"is_corresponding":false},{"id":1172429,"name":"Thao Trang Nguyen","orcid":null,"position":4,"is_corresponding":false},{"id":990047,"name":"David P Turicek","orcid":"0000-0003-0837-2688","position":5,"is_corresponding":false},{"id":258238,"name":"Lei Shi","orcid":"0000-0002-5312-8521","position":6,"is_corresponding":false},{"id":309494,"name":"Lixin Rui","orcid":null,"position":7,"is_corresponding":false},{"id":687814,"name":"James L. LaBelle","orcid":"0000-0001-6776-4695","position":8,"is_corresponding":false},{"id":277448,"name":"Christian M. Capitini","orcid":"0000-0002-2276-6731","position":9,"is_corresponding":false},{"id":606012,"name":"Sean Rinella","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:19:31.472087Z","pmid":"37333339","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}