{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T22:47:11Z","timestamp":1776120431683,"version":"3.50.1"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007224","name":"National Foundation for Science and Technology Development","doi-asserted-by":"publisher","award":["108.01-2020.02"],"award-info":[{"award-number":["108.01-2020.02"]}],"id":[{"id":"10.13039\/100007224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is the most aggressive hematopoietic malignancy characterized by uncontrolled proliferation of myeloid progenitor cells within the bone marrow. Tumor suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme, which suppresses inflammatory response in macrophages. Macrophages have a central role in the defense against foreign substances and circulating cancer cells by their professional phagocytic capacity. Little is known about contributions of CYLD to changes in biological properties of human macrophages and its involvement in AML. The present study, therefore, explored whether macrophage functions in healthy individuals and AML patients are influenced by CYLD. To this end, ninety-two newly diagnosed AML patients and 80 healthy controls were recruited. The mRNA expression levels of inflammation-related genes were evaluated by real-time PCR, cell maturation, phagocytosis and apoptosis assays by flow cytometry and secretion of inflammatory cytokines by ELISA. As a result, AML patients with the low CYLD expression were significantly higher in M4\/M5 than other subtypes according to the FAB type. The low CYLD expression was also closely associated with older patients and enhanced level of LDH in AML. Moreover, treatment of normal macrophages with CYLD siRNA enhanced activation of STAT-1, leading to increases in expressions of maturation markers and IL-6 production as well as suppression in cell apoptosis and phagocytosis, while macrophage phagocytosis from AML M4\/M5b was higher than that from healthy controls upon CYLD siRNA transfection through STAT1 signalling. In conclusion, the inhibitory effects of CYLD on macrophage functions are expected to affect the immune response in AML.<\/jats:p>","DOI":"10.1371\/journal.pone.0283586","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T17:29:48Z","timestamp":1691429388000},"page":"e0283586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["CYLD stimulates macrophage phagocytosis of leukemic cells through STAT1 signalling in acute myeloid leukemia"],"prefix":"10.1371","volume":"18","author":[{"given":"Nguyen Thanh","family":"Huyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-9209","authenticated-orcid":true,"given":"Nguyen Thy","family":"Ngoc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Hoang","family":"Giang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Thi","family":"Trang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ha Hong","family":"Hanh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Duc","family":"Binh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Van","family":"Giang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Xuan","family":"Canh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3494-5136","authenticated-orcid":true,"given":"Nguyen Thi","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"issue":"10","key":"pone.0283586.ref001","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1002\/ijc.25910","article-title":"Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia","volume":"129","author":"T Ikezoe","year":"2011","journal-title":"Int J Cancer"},{"issue":"24","key":"pone.0283586.ref002","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1038\/s41388-019-0757-y","article-title":"Lack of CD45 in FLT3-ITD mice results in a myeloproliferative phenotype, cortical porosity, and ectopic bone formation","volume":"38","author":"A Kresinsky","year":"2019","journal-title":"Oncogene"},{"issue":"1","key":"pone.0283586.ref003","doi-asserted-by":"crossref","first-page":"18630","DOI":"10.1038\/s41598-019-54901-9","article-title":"MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia","volume":"9","author":"ML Morales","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0283586.ref004","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ebiom.2017.11.013","article-title":"Mediator Kinase Phosphorylation of STAT1 S727 Promotes Growth of Neoplasms With JAK-STAT Activation","volume":"26","author":"II Nitulescu","year":"2017","journal-title":"EBioMedicine"},{"issue":"4","key":"pone.0283586.ref005","first-page":"318","article-title":"The Relationship between Fatigue and Cytokine Levels in Patients with Acute Myeloid Leukemia","volume":"12","author":"M Khosravi","year":"2018","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"pone.0283586.ref006","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cytogfr.2018.08.004","article-title":"The cytokine network in acute myeloid leukemia (AML): A focus on pro- and anti-inflammatory mediators","volume":"4","author":"S Binder","year":"2018","journal-title":"Cytokine Growth Factor Rev"},{"issue":"6","key":"pone.0283586.ref007","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/1097-0142(19800315)45:6<1365::AID-CNCR2820450615>3.0.CO;2-I","article-title":"Phagocytosis in acute leukemia","volume":"45","author":"L. 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