{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:16:48Z","timestamp":1767176208051,"version":"build-2238731810"},"update-to":[{"DOI":"10.12688\/f1000research.125877.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000}},{"DOI":"10.12688\/f1000research.125877.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000}}],"reference-count":29,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001297","name":"Royal College of Anaesthetists","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001297","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C36195\/A26770"],"award-info":[{"award-number":["C36195\/A26770"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UK and European Research Council","award":["STG 337066"],"award-info":[{"award-number":["STG 337066"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells. Methods NALM-6 and Reh cells were treated with propofol (5 and 10 \u03bcg\/ml) or sevoflurane (3.6%)\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    for six hours. Then, cells were harvested for adhesion assay and migration assay\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    . In\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    experiments, GFP-NALM-6 cells were pre-treated with propofol (10 \u03bcg\/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL\/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10\u03bcg\/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry. Results Both anaesthetics reduced\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    migration and\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy. Conclusion Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    and\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.125877.3","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:15:07Z","timestamp":1760001307000},"page":"1491","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["General anaesthetics reduce acute lymphoblastic leukaemia malignancies in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms"],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4789-8386","authenticated-orcid":false,"given":"Cui","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Gonzalez-Anton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Mi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingzhi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Lo Celso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1235-0537","authenticated-orcid":false,"given":"Daqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1541-1552","DOI":"10.1056\/NEJMra1400972","article-title":"Acute Lymphoblastic Leukemia in Children.","volume":"373","author":"S Hunger","year":"2015","journal-title":"N. 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Care Pain."},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.17268337","article-title":"General anaesthetics reduce acute lymphoblastic leukaemia malignancies in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms.","author":"J Cui","year":"2024"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:15:08Z","timestamp":1760001308000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":29,"URL":"https:\/\/doi.org\/10.12688\/f1000research.125877.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.125877.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.125877.1","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.138230.r158793, Koichi Yuki, Division of Cardiac Anesthesia, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, 26 Jan 2023, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/11-1491\/v1#referee-response-158793","order":0,"name":"referee-response-158793","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>cui jiang<\/b>; \n<i>Posted: 27 Feb 2023<\/i>; Thank this reviewer for their kind comments  Response  \n<b>Question 1:<\/b> We did acknowledge the longer exposure time is a limitation of the study. We have put in the discussion section: \u201c\n<i>Clinical doses of general anaesthetics for invasive procedures in adult patients are generally lower and shorter in duration for such procedures.<\/i>\u201d &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;  6 hours exposure time was chosen because:  We wish to do a proof-of-concept studies on whether long exposure time would yield significant results before designing shorter time period experiments given the how expensive it is to run such experiments. &nbsp; Although the initial half-life of propofol and sevoflurane is very short and patients recover from anaesthesia within minutes, the terminal half-life of propofol and sevoflurane can be theoretically long (4-7 hours for propofol reference: \n<i>Khurram Saleem Khan, FCAI FJFICMI, Ivan Hayes, FCAI FJFICMANZ, Donal J Buggy, MD MSc DME FRCPI FCAI FRCA, Pharmacology of anaesthetic agents I: intravenous anaesthetic agents,&nbsp;Continuing Education in Anaesthesia Critical Care &amp; Pain, Volume 14, Issue 3, June 2014, Pages 100\u2013105<\/i> and up to 20 hours for sevoflurane reference: \n<i>Clin Pharmacokinet 1999 Jan; 36 (1). Page 19). <\/i>Long terminal half life may&nbsp;hypothetically give time for general anaesthetics to act on leukaemia cells   With all being said, we did perform in vitro experiments measuring cellular parameters for other parallel studies e.g. protetin expressions and in vitro functional assays with shorter time period i.e. 2 hour; we could see significant cellular changes following 2 hours exposure time of propofol and sevoflurane; we may publish those results in the near future  \n<b>Question 2:<\/b> Recruitment of ALL to the bone marrow is the first step of the homing process which allow the disease to happen in this murine model \u2013 given these mice are not genetically modified to have ALL genes. Reduction of recruitment of ALL cells to bone marrow translates into reduction in homing hence lower possibility of disease-causing cells in bone marrow.","URL":"https:\/\/f1000research.com\/articles\/11-1491\/v3#referee-comment-9397","order":1,"name":"referee-comment-9397","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.162284.r246077, Paul M Maciocia, Jongwon Yoon, Department of Haematology, Cancer Institute, University College London, London, 09 Mar 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1491\/v2#referee-response-246077","order":2,"name":"referee-response-246077","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.162284.r273944, Victor H. Villar Cortes, School of medicine, University of St Andrews, St Andrews, Scotland, 25 May 2024, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-1491\/v2#referee-response-273944","order":3,"name":"referee-response-273944","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Royal College of Anaesthetists, London, UK and European Research Council (STG 337066), Brussels, Belgium and Cancer Research UK (C36195\/A26770), London, UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}