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However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three\u2010dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi\u2010omics analysis, including high\u2010throughput chromosome conformation capture (Hi\u2010C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21\u2010activated kinase 1 (PAK1). PAK1, which was up\u2010regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA\u20103 exerted an anti\u2010tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib\u2010sensitive and \u2010resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib\u2010resistant CLL.<\/jats:p>","DOI":"10.1002\/1878-0261.13281","type":"journal-article","created":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T23:44:29Z","timestamp":1657496669000},"page":"2920-2935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the significance of\n                    <scp>PAK1<\/scp>\n                    through chromosome conformation signatures in ibrutinib\u2010resistant chronic lymphocytic leukaemia"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-7858","authenticated-orcid":false,"given":"Zijuan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Hematology, Pukou CLL Center, Jiangsu Province Hospital The First Affiliated 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