{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:56:47Z","timestamp":1777928207498,"version":"3.51.4"},"reference-count":62,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n                    Imatinib (IM), a breakthrough in chronic myeloid leukemia (CML) treatment, is accompanied by discontinuation challenges owing to drug intolerance. Although\n                    <jats:italic toggle=\"yes\">BCR-ABL1<\/jats:italic>\n                    mutation is a key cause of CML resistance, understanding mechanisms independent of\n                    <jats:italic toggle=\"yes\">BCR-ABL1<\/jats:italic>\n                    is also important. This study investigated the sphingosine-1-phosphate (S1P) signaling-associated genes (\n                    <jats:italic toggle=\"yes\">SphK1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">S1PRs<\/jats:italic>\n                    ) and their role in BCR-ABL1-independent resistant CML, an area currently lacking investigation. Through comprehensive transcriptomic analysis of IM-sensitive and IM-resistant CML groups, we identified the differentially expressed genes and found a notable upregulation of\n                    <jats:italic toggle=\"yes\">SphK1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">S1PR2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">S1PR5<\/jats:italic>\n                    in IM-resistant CML. Functional annotation revealed their roles in critical cellular processes such as proliferation and GPCR activity. Their network analysis uncovered significant clusters, emphasizing the interconnectedness of the S1P signaling genes. Further, we identified interactors such as\n                    <jats:italic toggle=\"yes\">BIRC3<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">TRAF6<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">SRC<\/jats:italic>\n                    genes, with potential implications for IM resistance. Additionally, receiver operator characteristic curve analysis suggested these genes\u2019 potential as biomarkers for predicting IM resistance. Network pharmacology analysis identified six herbal compounds\u2014ampelopsin, ellagic acid, colchicine, epigallocatechin-3-gallate, cucurbitacin B, and evodin\u2014as potential drug candidates targeting the S1P signaling genes. In summary, this study contributes to efforts to better understand the molecular mechanisms underlying BCR-ABL1-independent CML resistance. Moreover, the S1P signaling genes are promising therapeutic targets and plausible new innovation avenues to combat IM resistance in cancer clinical care in the future.\n                  <\/jats:p>","DOI":"10.1089\/omi.2024.0074","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T16:33:40Z","timestamp":1720629220000},"page":"367-376","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["S1P Signaling Genes as Prominent Drivers of BCR-ABL1-Independent Imatinib Resistance and Six Herbal Compounds as Potential Drugs for Chronic Myeloid Leukemia"],"prefix":"10.1177","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-8669","authenticated-orcid":false,"given":"Sikha","family":"Morang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manisha","family":"Bisht","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of AYUSH, All India Institute of Medical Sciences, Rishikesh, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surabhi","family":"Thapliyal","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech, Blacksburg, United States."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailendra","family":"Handu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh, 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