Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients.

Autor: Venton G; APHM, Hôpital de la Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.; TAGC-Theories and Approaches of Genomic Complexity, Aix Marseille University, Marseille, France., Colle J; APHM, Hôpital de la Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.; TAGC-Theories and Approaches of Genomic Complexity, Aix Marseille University, Marseille, France., Tichadou A; APHM, Hôpital de la Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.; TAGC-Theories and Approaches of Genomic Complexity, Aix Marseille University, Marseille, France., Quessada J; APHM, Hôpital La Timone, Laboratoire d'Hématologie, Marseille, France., Baier C; Advanced BioDesign, Lyon, France., Labiad Y; Advanced BioDesign, Lyon, France., Perez M; Advanced BioDesign, Lyon, France., De Lassus L; APHM, Hôpital de la Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France., Loosveld M; APHM, Hôpital La Timone, Laboratoire d'Hématologie, Marseille, France.; CRCM, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, Marseille, France., Arnoux I; APHM, Hôpital La Timone, Laboratoire d'Hématologie, Marseille, France., Abbou N; APHM, Hopital La Timone, Service d'Oncobiologie, Plateforme M2GM, Hopital de la Timone, Marseille, France.; Aix-Marseille Univ, INSERM, INRAE, C2VN, Laboratory of Haematology, CRB Assistance Publique-Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France., Ceylan I; Advanced BioDesign, Lyon, France., Martin G; Advanced BioDesign, Lyon, France., Costello R; APHM, Hôpital de la Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.; TAGC-Theories and Approaches of Genomic Complexity, Aix Marseille University, Marseille, France.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Oct; Vol. 28 (19), pp. e70011.
DOI: 10.1111/jcmm.70011
Abstrakt: Acute myeloid leukaemia (AML) remains a major unmet medical, despite recent progress in targeted molecular therapies. One aspect of leukaemic cell resistance to chemotherapy is the development of clones with increased capacity to respond to cellular stress and the production of reactive oxygen species (ROS), thanks in particular to a high aldehyde dehydrogenases (ALDH) 1A1/2 activity. At diagnosis, ROS level and ALDH1A1/2 activity in AML patients BM are correlated with the different ELN 2022 prognostic groups and overall survival (OS). A significant lower ALDH1A1/2 activity in BM was observed in the favourable ELN2022 subgroup compared to the intermediate and adverse group (p < 0.01). In the same way, the ROS levels were significantly lower in the favourable ELN 2022 subgroup compared to the intermediate group (p < 0.0001) and adverse group (p < 0.0002). ROS high AML patients had a significantly lower median overall survival (OS) (8.2 months) than ROS low patients (24.6 months) (p = 0.0368). After first-line therapy, a significant increase of ROS level (p = 0.015) and ALDH1A1/2 activity (0 = 0.0273) in leukaemic blasts was observed, especially in the refractory ones. ABD-3001, a competitive and irreversible inhibitor of ALDHs 1 and 3, can in vitro inhibit the proliferation of patient-derived leukaemic cells in accordance with redox balance. In multivariate analysis, ROS level was the most significant (p < 0.05) and the strongest predictive factor for the sensitivity of cells to ABD-3001. The safety profile of ABD-3001 is currently being assessed through the first inhuman multicenter phase 1 clinical trial "ODYSSEY" (NCT05601726) for patients with relapsed AML.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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