British journal of cancer · 2026
HDAC6 is a biomarker of leukaemic dissemination and relapse in B-ALL.
СтатьяНазвание и аннотация: Перевод в очереди
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Jiménez-Camacho Karina E, Vargas-Robles Hilda, Adomako Joseph, Sánchez-Argáez Ana Beatriz, Correa-Lara M Victor M, Sandoval-Cabrera Antonio, Dorantes-Acosta Elisa, Mejía-Aranguré Juan Manuel, Castañeda-Contreras Sara, Núñez-Enríquez Juan Carlos, Mata-Rocha Minerva, Pelayo Rosana, Schnoor Michael
Аннотация
BACKGROUND/OBJECTIVES: Relapse remains the leading cause of treatment failure in B-cell acute lymphoblastic leukaemia (B-ALL), highlighting the need for biomarkers and therapeutic targets that limit leukaemic dissemination. We investigated whether histone deacetylase 6 (HDAC6), a regulator of cortactin-dependent actin remodelling, contributes to B-ALL progression and relapse.
SUBJECTS/METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
SUBJECTS/METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.