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We investigated whether histone deacetylase 6 (HDAC6), a regulator of cortactin-dependent actin remodelling, contributes to B-ALL progression and relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects\/Methods<\/jats:title>\n                    <jats:p>HDAC6 expression was analysed in cohorts of 72 paediatric and 54 adult patients with B-ALL and validated in B-ALL cell lines. The functional role of HDAC6 was assessed using pharmacological inhibition and shRNA-mediated knockdown in assays of CXCL12-induced actin remodelling, transendothelial migration, bone marrow colonisation and leukaemic dissemination in vivo. Cortactin-depleted cells were used to determine pathway dependence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HDAC6 expression was elevated in B-ALL cell lines and patient samples and was significantly associated with relapse in both patient cohorts. Pharmacological inhibition or genetic depletion of HDAC6 impaired CXCL12-induced actin remodelling, transendothelial migration, bone marrow colonisation and leukaemic dissemination. HDAC6 inhibition failed to further reduce migration in cortactin-deficient cells, indicating that HDAC6 promotes leukaemic motility through cortactin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HDAC6 is a clinically relevant biomarker associated with B-ALL relapse and a critical regulator of cortactin-dependent leukaemic dissemination. Targeting HDAC6 represents a promising therapeutic strategy to limit tissue invasion and reduce relapse.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03539-2","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:35:57Z","timestamp":1785026157000},"page":"1470-1482","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HDAC6 is a biomarker of leukaemic dissemination and relapse in B-ALL"],"prefix":"10.1038","volume":"135","author":[{"given":"Karina E.","family":"Jim\u00e9nez-Camacho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Vargas-Robles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0291-9365","authenticated-orcid":false,"given":"Joseph","family":"Adomako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"S\u00e1nchez-Arg\u00e1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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