{"doi":"10.1200/po.23.00302","title":"Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay","abstract":"PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry-based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs' components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DC's most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples.","journal":"JCO Precision Oncology","year":2023,"id":368355,"datarank":0.2533877438570111,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.011972056991896065,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.011972056991896065,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9628,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00025038"]},"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":1126737,"name":"Christine Gu","orcid":null,"position":1,"is_corresponding":false},{"id":512093,"name":"Michelle Richardson","orcid":"0000-0002-6029-0949","position":2,"is_corresponding":false},{"id":1126300,"name":"Ryosuke Kita","orcid":"0000-0003-4526-5275","position":3,"is_corresponding":false},{"id":1126738,"name":"Marianne T. Santaguida","orcid":null,"position":4,"is_corresponding":false},{"id":1126301,"name":"Kamran A. Ali","orcid":"0009-0006-6811-6175","position":5,"is_corresponding":false},{"id":1126739,"name":"Debbie Strachan","orcid":null,"position":6,"is_corresponding":false},{"id":1126302,"name":"Anukriti Dhar","orcid":"0000-0003-0788-397X","position":7,"is_corresponding":false},{"id":1126740,"name":"George Yam","orcid":null,"position":8,"is_corresponding":false},{"id":767676,"name":"Wade Anderson","orcid":null,"position":9,"is_corresponding":false},{"id":234618,"name":"Erica Anderson","orcid":null,"position":10,"is_corresponding":false},{"id":1037551,"name":"Juwita Hübner","orcid":null,"position":11,"is_corresponding":false},{"id":273631,"name":"Sarah K. Tasian","orcid":"0000-0003-1327-1662","position":12,"is_corresponding":false},{"id":301504,"name":"Mignon L. Loh","orcid":"0000-0003-4099-4700","position":13,"is_corresponding":false},{"id":817117,"name":"Markus D. Lacher","orcid":"0000-0003-2597-5704","position":14,"is_corresponding":false},{"id":317922,"name":"Elliot Stieglitz","orcid":"0000-0001-7032-4623","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:15:20.453499Z","pmid":"37944074","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":[]}