{"doi":"10.1111/bjh.70180","title":"Addition of hydroxyurea (hydroxycarbamide) enhances the efficacy of fludarabine/cytarabine‐based salvage regimens against acute myeloid leukaemia","abstract":"Despite intensive treatment, patients with relapsed or refractory acute myeloid leukaemia (AML) have a dismal prognosis. A cornerstone therapy for relapsed/refractory AML is a combination of fludarabine (F-ara-A) and cytarabine (ara-C), so-called FLA. As the enzyme SAMHD1 mediates resistance to both ara-C and F-ara-A, we investigated whether SAMHD1 inhibition via hydroxyurea (hydroxycarbamide; HU) could improve FLA efficacy. Here, we show that HU synergistically enhanced ara-C-, F-ara-A- and FLA-induced cytotoxicity in an SAMHD1-dependent manner in AML cell lines, primary AML cells and an immunocompetent AML mouse model. Mechanistically, HU significantly increased the active metabolite triphosphates of ara-C and F-ara-A in FLA combinations. Furthermore, leukaemic SAMHD1 protein expression negatively correlated with overall survival in a cohort of FLA-treated refractory AML patients. Our findings suggest that the addition of HU improves the efficacy of FLA-based regimens and warrant clinical trials to test the safety and efficacy of this combination in patients with relapsed/refractory AML.","journal":"British Journal of Haematology","year":2025,"id":554248,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":248189,"name":"Sijia Tao","orcid":null,"position":1,"is_corresponding":false},{"id":17530,"name":"Christer Nilsson","orcid":"0000-0003-0695-0050","position":2,"is_corresponding":false},{"id":1451507,"name":"Elory Leonard","orcid":"0009-0004-7249-2849","position":3,"is_corresponding":false},{"id":1451508,"name":"Runqing Zhang","orcid":"0009-0001-0746-5594","position":4,"is_corresponding":false},{"id":1452082,"name":"Agnes L. 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