{"doi":"10.1016/j.celrep.2021.109386","title":"TNF-α-induced alterations in stromal progenitors enhance leukemic stem cell growth via CXCR2 signaling","abstract":"Chronic myeloid leukemia (CML) is propagated by leukemia stem cells (LSCs) that are not eradicated by tyrosine kinase inhibitor (TKI) treatment and persist as a source of disease recurrence. Bone marrow (BM) mesenchymal niches play an essential role in hematopoietic stem cell (HSC) and LSC maintenance. Using a murine CML model, we examine leukemia-induced alterations in mesenchymal cell populations. We show that 6C3+ stromal progenitors expand in CML BM and exhibit increased LSC but reduced HSC supportive capacity. Tumor necrosis factor alpha (TNF-α) signaling mediates expansion and higher expression of CXCL1 in CML BM 6C3+ cells and higher expression of the CXCL1 receptor CXCR2 in LSCs. CXCL1 enhances LSC proliferation and self-renewal, whereas CXCR2 inhibition reduces LSC growth and enhances LSC targeting in combination with tyrosine kinase inhibitors (TKIs). We find that TNF-α-mediated alterations in CML BM stromal niches enhance support of LSC maintenance and growth via CXCL1-CXCR2 signaling and that CXCR2 inhibition effectively depletes CML LSCs.","journal":"Cell Reports","year":2021,"id":165409,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":360952,"name":"Hui Li","orcid":"0000-0002-4837-7515","position":1,"is_corresponding":false},{"id":329281,"name":"Kwangmin Choi","orcid":"0000-0003-4671-962X","position":2,"is_corresponding":false},{"id":467523,"name":"Kathleen Hueneman","orcid":"0000-0002-6194-3569","position":3,"is_corresponding":false},{"id":688978,"name":"Jianbo He","orcid":"0000-0002-0623-9763","position":4,"is_corresponding":false},{"id":339192,"name":"Robert S. Welner","orcid":"0000-0003-2498-9469","position":5,"is_corresponding":false},{"id":467530,"name":"Daniel T. Starczynowski","orcid":"0000-0002-5771-7462","position":6,"is_corresponding":false},{"id":253492,"name":"Ravi Bhatia","orcid":"0000-0001-5740-2316","position":7,"is_corresponding":false},{"id":457633,"name":"Puneet Agarwal","orcid":"0000-0003-1688-3840","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:45:40.838485Z","pmid":"34260914","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":[]}