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The cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1A1) is underexpressed in AML cells when compared to healthy cells, both at the RNA level and at the protein level, and at least in the former, both in the bone marrow and in peripheral blood. Nonetheless, ALDH1A1\/ALDH1A2 activity increases in AML cells during disease relapse and is higher in adverse prognosis AML in comparison with favorable prognosis AML. Furthermore, especially in relapsed AML and in unfavorable AML, AML cells rich in ALDH1A1 can contain high levels of reactive oxygen species (ROS), in parallel with high ALDH1A1\/2 activity. This metabolic feature is clearly incompatible with normal stem cells. The term \u201cstem-like\u201d therefore is useful to coin malignant cells with a variety of genetic makeups, metabolic programming and biomarkers that converge in the function of survival of clones sufficient to sustain, spread and re-establish neoplastic disease. Therefore, AML \u201cstem-like\u201d cells survive cancer treatment that eradicates other malignant cell clones. This fact differentiates AML \u201cstem-like\u201d cells from normal stem and progenitor cells that function in tissue regeneration as part of a distinct hierarchical order of cell phenotypes. The ODYSSEY clinical trial is a Phase I\/II study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABD-3001, a novel therapeutic agent, in patients with AML who have relapsed or are refractory to standard treatments. In this context, ABD-3001 is used as an inhibitor of cytosolic ALDH1 enzymes, such as ALDH1A1 and ALDH1A2.<\/jats:p>","DOI":"10.3390\/cells14131038","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:19:27Z","timestamp":1751887167000},"page":"1038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"14","author":[{"given":"R\u00e9gis","family":"Costello","sequence":"first","affiliation":[{"name":"APHM, Hematology and Cellular Therapy Department, Conception Hospital, 13005 Marseille, France"},{"name":"TAGC-Theories and Approaches of Genomic Complexity, INSERM, UMR1090, Parc Scientifique de Luminy, Aix Marseille University, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-8641","authenticated-orcid":false,"given":"Garrett M.","family":"Dancik","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Eastern Connecticut State University, Willimantic, CT 06226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00efs","family":"Dubiau","sequence":"additional","affiliation":[{"name":"TAGC-Theories and Approaches of Genomic Complexity, INSERM, UMR1090, Parc Scientifique de Luminy, Aix Marseille University, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6870-3712","authenticated-orcid":false,"given":"Lamia","family":"Madaci","sequence":"additional","affiliation":[{"name":"TAGC-Theories and Approaches of Genomic Complexity, INSERM, UMR1090, Parc Scientifique de Luminy, Aix Marseille University, 13009 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-3863","authenticated-orcid":false,"given":"Spiros","family":"Vlahopoulos","sequence":"additional","affiliation":[{"name":"First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, Goudi, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107985","DOI":"10.1016\/j.pharmthera.2021.107985","article-title":"Cell Plasticity, Senescence, and Quiescence in Cancer Stem Cells: Biological and Therapeutic Implications","volume":"231","author":"Paul","year":"2022","journal-title":"Pharmacol. 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