{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:50:25Z","timestamp":1790855425303,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022QH142"],"award-info":[{"award-number":["ZR2022QH142"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical and Health Technology Development Plan Project of Shandong Province","award":["202203040348"],"award-info":[{"award-number":["202203040348"]}]},{"name":"Research Project of Weifang Municipal Health Commission","award":["WFWSJK-2023-035"],"award-info":[{"award-number":["WFWSJK-2023-035"]}]},{"name":"Beijing Norman Bethune Public Welfare Foundation"},{"name":"Exploration and Research Fund for Diagnosis and Treatment of Hematological Tumors","award":["XYZL-003"],"award-info":[{"award-number":["XYZL-003"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202427"],"award-info":[{"award-number":["82202427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxia-associated hydrogen sulfide (H2S) accumulation promotes chemotherapy resistance in solid tumor cells. This study delved into the mechanism by which cystathionine \u03b2\u2013synthase (CBS)\/H2S signaling is involved in the development of acute myeloid leukemia (AML) resistance to cytarabine (ara-C) under hypoxic conditions. The levels of CBS and H2S in AML cells and ara-C-resistant AML cells were evaluated. Subsequently, the expression of CBS and H2S under normoxic and hypoxic conditions in ara-C-resistant AML cells was further scrutinized. sh-CBS or sh-thrombospondin 1 (THBS1) was transfected into ara-C-resistant AML cells, which were then exposed to 1% oxygen and\/or ara-C. The cell viability, apoptosis, and lipid metabolism level were evaluated by the cell counting kit-8, flow cytometry, kit, and qPCR. Simultaneously, the methylation of THBS1 was detected via methylation-specific PCR analysis. The expression of CBS and H2S is elevated in ara-C-resistant AML cells, rising proportionally with diminishing oxygen concentration. In ara-C-resistant AML cells, hypoxia stimulated cell viability, suppressed apoptosis, augmented total cholesterol and triacylglycerol levels, upregulated the levels of CD36 and carnitine palmitoyltransferase-1\u03b1, as well as downregulated short-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor \u03b1 levels, while these effects of hypoxia were all reversed by sh-CBS. sh-CBS notably decreases the hypermethylation level of THBS1 in ara-C-resistant AML cells. sh-THBS1 reversed the regulatory effect of sh-CBS on lipid metabolism, cell viability, and apoptosis in ara-C-resistant AML cells. Conversely, sh-CD36 effectively overrode the reversal impact of sh-THBS1. Activation of CBS\/H2S signaling in a hypoxic environment participates in the ara-C resistance of AML cells by facilitating CD36-mediated fatty acid metabolism through the mediation of THBS1 methylation.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf065","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:57:37Z","timestamp":1747295857000},"source":"Crossref","is-referenced-by-count":7,"title":["Hypoxia-activated cystathionine \u03b2-synthase\/H2S signaling drives drug resistance in acute myeloid leukemia through CD36-mediated fatty acid metabolism"],"prefix":"10.1093","volume":"117","author":[{"given":"Qianpeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Hematology, Weifang People's Hospital, Shandong Second Medical University , No. 151 Yuhe Road, Guangwen Street, Kuiwen District, Weifang, Shandong Province 261000 ,","place":["P.R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University , No. 2428 Yuhe Road, Kuiwen District, Weifang, Shandong Province 261000 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Weifang People's Hospital, Shandong Second Medical University , No. 151 Yuhe Road, Guangwen Street, Kuiwen District, Weifang, Shandong Province 261000 ,","place":["P.R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Hematology, Weifang People's Hospital, Shandong Second Medical University , No. 151 Yuhe Road, Guangwen Street, Kuiwen District, Weifang, Shandong Province 261000 ,","place":["P.R. 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