{"doi":"10.1182/blood.2022018512","title":"Haplodeficiency of the 9p21 tumor suppressor locus causes myeloid disorders driven by the bone marrow microenvironment","abstract":"The chromosome 9p21 locus comprises several tumor suppressor genes including MTAP, CDKN2A, and CDKN2B, and its homo- or heterozygous deletion is associated with reduced survival in multiple cancer types. We report that mice with germ line monoallelic deletion or induced biallelic deletion of the 9p21-syntenic locus (9p21s) developed a fatal myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)-like disease associated with aberrant trabecular bone formation and/or fibrosis in the bone marrow (BM). Reciprocal BM transfers and conditional targeting of 9p21s suggested that the disease originates in the BM stroma. Single-cell analysis of 9p21s-deficient BM stroma revealed the expansion of chondrocyte and osteogenic precursors, reflected in increased osteogenic differentiation in vitro. It also showed reduced expression of factors maintaining hematopoietic stem/progenitor cells, including Cxcl12. Accordingly, 9p21s-deficient mice showed reduced levels of circulating Cxcl12 and concomitant upregulation of the profibrotic chemokine Cxcl13 and the osteogenesis- and fibrosis-related multifunctional glycoprotein osteopontin/Spp1. Our study highlights the potential of mutations in the BM microenvironment to drive MDS/MPN-like disease.","journal":"Blood","year":2023,"id":360741,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"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":1112542,"name":"Pei-Feng Hsu","orcid":"0000-0001-9749-7591","position":1,"is_corresponding":false},{"id":581436,"name":"Eduardo Esteva","orcid":"0000-0002-7223-6632","position":2,"is_corresponding":false},{"id":886902,"name":"Rossella Labella","orcid":"0000-0002-3768-9273","position":3,"is_corresponding":false},{"id":309135,"name":"Yueyang Wang","orcid":"0000-0002-8456-1440","position":4,"is_corresponding":false},{"id":259273,"name":"Alireza Khodadadi‐Jamayran","orcid":"0000-0003-2495-7504","position":5,"is_corresponding":false},{"id":247619,"name":"Joseph N. Pucella","orcid":"0000-0003-0875-8046","position":6,"is_corresponding":false},{"id":1112997,"name":"Cynthia Z. Liu","orcid":null,"position":7,"is_corresponding":false},{"id":459617,"name":"Arnaldo Arbini","orcid":"0000-0003-0345-4174","position":8,"is_corresponding":false},{"id":69214,"name":"Aristotelis Tsirigos","orcid":"0000-0002-7512-8477","position":9,"is_corresponding":false},{"id":278875,"name":"Stavroula Kousteni","orcid":"0000-0001-5163-3551","position":10,"is_corresponding":false},{"id":247624,"name":"Boris Reizis","orcid":"0000-0003-1140-7853","position":11,"is_corresponding":false},{"id":849759,"name":"Jue Feng","orcid":"0000-0002-2506-1294","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:06.433417Z","pmid":"37267505","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":[]}