{"doi":"10.1101/2024.06.28.601274","title":"Integrin-deficient T cell leukemia accumulates in the central nervous system","abstract":"T-cell acute lymphoblastic leukemia (T-ALL) spreads aggressively to the central nervous system (CNS), particularly the leptomeninges. Children with T-ALL are treated with high-dose, CNS-directed chemotherapy, which can cause lasting neurotoxicity and is not always effective. Little is known about how T-ALL enters and persists within the CNS. However, normal T cell migration into the CNS has been extensively studied. Two integrins-VLA-4 and LFA-1-mediate normal T cell entry to the CNS, and VLA-4 blockade effectively treats multiple sclerosis by excluding T cells from the brain. We hypothesized that these integrins would likewise be required for T-ALL CNS entry. Unexpectedly, not only were VLA-4 and LFA-1 dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control. Mechanistically, integrin loss accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space. Integrin blockade synergized with chemotherapy targeting proliferating cells, raising the possibility that combination therapy might be a powerful strategy.","journal":"eLife","year":2024,"id":500434,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279463,"name":"Cynthia Chen","orcid":"0000-0003-4604-2241","position":1,"is_corresponding":false},{"id":701477,"name":"Bibi S. Subhan","orcid":null,"position":2,"is_corresponding":false},{"id":1349736,"name":"Hyunsoo Chung","orcid":"0000-0001-5159-357X","position":3,"is_corresponding":false},{"id":676106,"name":"Martyna Okuniewska","orcid":null,"position":4,"is_corresponding":false},{"id":1350083,"name":"Asha Y Caslin","orcid":null,"position":5,"is_corresponding":false},{"id":849425,"name":"Kathleen A. Martin","orcid":"0000-0002-5544-2127","position":6,"is_corresponding":false},{"id":279212,"name":"Jennifer K. Schiavo","orcid":"0000-0001-8644-8428","position":7,"is_corresponding":false},{"id":1349737,"name":"Jonah Vernejoul","orcid":"0000-0003-4915-4468","position":8,"is_corresponding":false},{"id":123952,"name":"Robert C Froemke","orcid":"0000-0002-1230-6811","position":9,"is_corresponding":false},{"id":325605,"name":"Michael Cammer","orcid":"0000-0003-4930-1739","position":10,"is_corresponding":false},{"id":260724,"name":"Susan R. Schwab","orcid":"0000-0002-0834-0822","position":11,"is_corresponding":false},{"id":527201,"name":"Samantha Y. Lux","orcid":"0000-0001-9749-1616","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:10:08.435215Z","pmid":"41867713","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":[]}