{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:38:00Z","timestamp":1790656680580,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["1708085MH223"],"award-info":[{"award-number":["1708085MH223"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although tyrosine kinase inhibitors (TKIs), including imatinib, have greatly improved clinical treatment of patients with chronic myeloid leukemia (CML), drug resistance remains a major obstacle. Studies on the mechanisms underlying imatinib resistance and other alternative drugs are urgently needed. Liquid chromatography tandem mass spectrometry was applied to investigate the differences in proteomics and phosphoproteomics between K562 and K562\/G (imatinib resistant K562). Multiple bioinformatics analyses were performed to unveil the differential signal pathways. CCK\u20108 was used to detect cell proliferation. Flow cytometry was performed to analyze reactive oxygen species (ROS), cell cycle, and cell apoptosis. Western blotting and quantitative real\u2010time reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) were used to observe the changes of ROS and autophagy associated with imatinib resistance in CML. Our results indicated that ROS\u2010autophagy formed one negative feedback loop and was associated with imatinib resistance. Additionally, the limited\u2010rate enzymes of serine synthesis pathway were escalated in K562\/G, which could contribute to the increased cyclin\u2010dependent kinases and cell proliferation index. According to phosphoproteomics data, K562\/G cells exhibited abnormal phosphorylation of splicing signals. These results revealed that it could be one useful strategy to correct metabolism shift and oxidative stress, or moderately regulate autophagy. Future research should focus on the discovery of potential targets in ROS\u2010autophagy loop.<\/jats:p>","DOI":"10.1002\/pmic.202100094","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T11:20:39Z","timestamp":1632655239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteomics analysis reveals the correlation of programmed ROS\u2010autophagy loop and dysregulated G1\/S checkpoint with imatinib resistance in chronic myeloid leukemia cells"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiucai","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-9516","authenticated-orcid":false,"given":"Shihong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingli","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Lin","sequence":"additional","affiliation":[{"name":"Wannan Medical College  Wuhu Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03309-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.174060"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/shem.2003.50034"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24066"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-335497"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-696013"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3317"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-183665"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.168"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.51"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079478"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2017.11.011"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7977"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-4-6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.247"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-739086"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.108"},{"key":"e_1_2_10_19_1","first-page":"1","article-title":"Reactive oxygen species in BCR\u2010ABL1\u2010expressing cells \u2013 relevance to chronic myeloid leukemia","volume":"64","author":"Antoszewska\u2010Smith J.","year":"2017","journal-title":"Acta Biochimica Polonica"},{"key":"e_1_2_10_20_1","first-page":"455","article-title":"Persistent STAT5\u2010mediated ROS production and involvement of aberrant p53 apoptotic signaling in the resistance of chronic myeloid leukemia to imatinib","volume":"41","author":"Cheng Y.","year":"2018","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1543875"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.07.006"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-666214"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36267-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07868-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.11.014"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1053-y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10350"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1589"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-3291"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0603708"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200701035"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1644913"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.506"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2016.01.010"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2010.09.010"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-015-1135-z"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.264"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0252-4"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.01.039"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25196"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.214155"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.21037\/sci.2017.01.06"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-04-843771"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.318"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06063-x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw936"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.202100094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pmic.202100094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.202100094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:27:36Z","timestamp":1761067656000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.202100094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":47,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/pmic.202100094"],"URL":"https:\/\/doi.org\/10.1002\/pmic.202100094","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]},"assertion":[{"value":"2021-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2100094"}}