{"doi":"10.1126/sciadv.aba5536","title":"Leukemia-on-a-chip: Dissecting the chemoresistance mechanisms in B cell acute lymphoblastic leukemia bone marrow niche","abstract":"B cell acute lymphoblastic leukemia (B-ALL) blasts hijack the bone marrow (BM) microenvironment to form chemoprotective leukemic BM \"niches,\" facilitating chemoresistance and, ultimately, disease relapse. However, the ability to dissect these evolving, heterogeneous interactions among distinct B-ALL subtypes and their varying BM niches is limited with current in vivo methods. Here, we demonstrated an in vitro organotypic \"leukemia-on-a-chip\" model to emulate the in vivo B-ALL BM pathology and comparatively studied the spatial and genetic heterogeneity of the BM niche in regulating B-ALL chemotherapy resistance. We revealed the heterogeneous chemoresistance mechanisms across various B-ALL cell lines and patient-derived samples. We showed that the leukemic perivascular, endosteal, and hematopoietic niche-derived factors maintain B-ALL survival and quiescence (e.g., CXCL12 cytokine signal, VCAM-1/OPN adhesive signals, and enhanced downstream leukemia-intrinsic NF-κB pathway). Furthermore, we demonstrated the preclinical use of our model to test niche-cotargeting regimens, which may translate to patient-specific therapy screening and response prediction.","journal":"Science Advances","year":2020,"id":55988,"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":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247435,"name":"Matthew T. Witkowski","orcid":"0000-0003-1434-4288","position":1,"is_corresponding":false},{"id":293260,"name":"Jacob Harris","orcid":null,"position":2,"is_corresponding":false},{"id":238065,"name":"Igor Dolgalev","orcid":"0000-0003-4451-126X","position":3,"is_corresponding":false},{"id":247440,"name":"Sheetal Sreeram","orcid":"0000-0001-8031-9617","position":4,"is_corresponding":false},{"id":290727,"name":"Weiyi Qian","orcid":"0000-0002-5260-8515","position":5,"is_corresponding":false},{"id":290728,"name":"Jie Tong","orcid":"0000-0002-7138-0886","position":6,"is_corresponding":false},{"id":290729,"name":"Xin Chen","orcid":"0000-0002-2547-2915","position":7,"is_corresponding":false},{"id":109597,"name":"Iannis Aifantis","orcid":"0000-0001-6857-1035","position":8,"is_corresponding":false},{"id":247451,"name":"Weiqiang Chen","orcid":"0000-0002-9469-8328","position":9,"is_corresponding":false},{"id":247437,"name":"Chao Ma","orcid":"0000-0002-1023-1326","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T21:05:49.581291Z","pmid":"33127669","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":[]}