{"doi":"10.1016/j.celrep.2023.112794","title":"Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells","abstract":"Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ 12 -PGJ 2 , and 15d-PGJ 2 , which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic analysis of GPR44 −/− LICs indicated that GPR44 activation by CyPGs suppressed KRAS-mediated MAPK and PI3K/AKT/mTOR signaling pathways, to enhance apoptosis. Our studies show the role of GPR44, providing mechanistic underpinnings of the chemopreventive and chemotherapeutic properties of selenium and CyPGs in AML.","journal":"Cell Reports","year":2023,"id":364227,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":377514,"name":"Shaneice K. Nettleford","orcid":null,"position":1,"is_corresponding":false},{"id":777258,"name":"Jiayan Zhou","orcid":"0000-0001-5974-087X","position":2,"is_corresponding":false},{"id":375973,"name":"Brooke E. Arner","orcid":"0000-0001-7844-0979","position":3,"is_corresponding":false},{"id":777257,"name":"Molly A. Hall","orcid":"0000-0001-7740-401X","position":4,"is_corresponding":false},{"id":402547,"name":"Arati Sharma","orcid":"0000-0001-7178-949X","position":5,"is_corresponding":false},{"id":402540,"name":"Charyguly Annageldiyev","orcid":"0000-0003-0293-7203","position":6,"is_corresponding":false},{"id":1119451,"name":"R. Rossi","orcid":null,"position":7,"is_corresponding":false},{"id":350286,"name":"Diwakar Bastihalli Tukaramrao","orcid":"0000-0002-9503-3424","position":8,"is_corresponding":false},{"id":1119452,"name":"Deborpita Sarkar","orcid":null,"position":9,"is_corresponding":false},{"id":416625,"name":"Shailaja Hegde","orcid":"0000-0001-8228-9570","position":10,"is_corresponding":false},{"id":1119453,"name":"Ujjawal H. Gandhi","orcid":null,"position":11,"is_corresponding":false},{"id":446321,"name":"Emily R. Finch","orcid":null,"position":12,"is_corresponding":false},{"id":1119454,"name":"Laura L. Goodfield","orcid":null,"position":13,"is_corresponding":false},{"id":1119455,"name":"Michael D. Quickel","orcid":null,"position":14,"is_corresponding":false},{"id":402546,"name":"David F. Claxton","orcid":"0000-0001-9209-2405","position":15,"is_corresponding":false},{"id":274990,"name":"Robert F. Paulson","orcid":"0000-0001-5923-5128","position":16,"is_corresponding":false},{"id":350287,"name":"K. Sandeep Prabhu","orcid":"0000-0003-0644-1512","position":17,"is_corresponding":false},{"id":352055,"name":"Fenghua Qian","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T01:14:36.728255Z","pmid":"37459233","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":[]}