Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia

In acute myeloid leukemia (AML) it is important to elucidate the biological events that lead from remission to relapse, which have a high probability of leading to an adverse disease outcome. The cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1A1) is underexpressed in AML cells when compared...

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Main Authors: Régis Costello, Garrett M. Dancik, Anaïs Dubiau, Lamia Madaci, Spiros Vlahopoulos
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/13/1038
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author Régis Costello
Garrett M. Dancik
Anaïs Dubiau
Lamia Madaci
Spiros Vlahopoulos
author_facet Régis Costello
Garrett M. Dancik
Anaïs Dubiau
Lamia Madaci
Spiros Vlahopoulos
author_sort Régis Costello
collection DOAJ
description In acute myeloid leukemia (AML) it is important to elucidate the biological events that lead from remission to relapse, which have a high probability of leading to an adverse disease outcome. 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 “stem-like” 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 “stem-like” cells survive cancer treatment that eradicates other malignant cell clones. This fact differentiates AML “stem-like” 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.
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spelling doaj-art-d0d0d0432c5d4e6c8f2fc3c29d330fe62025-07-11T14:37:58ZengMDPI AGCells2073-44092025-07-011413103810.3390/cells14131038Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid LeukemiaRégis Costello0Garrett M. Dancik1Anaïs Dubiau2Lamia Madaci3Spiros Vlahopoulos4APHM, Hematology and Cellular Therapy Department, Conception Hospital, 13005 Marseille, FranceDepartment of Computer Science, Eastern Connecticut State University, Willimantic, CT 06226, USATAGC-Theories and Approaches of Genomic Complexity, INSERM, UMR1090, Parc Scientifique de Luminy, Aix Marseille University, 13009 Marseille, FranceTAGC-Theories and Approaches of Genomic Complexity, INSERM, UMR1090, Parc Scientifique de Luminy, Aix Marseille University, 13009 Marseille, FranceFirst Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, Goudi, 11527 Athens, GreeceIn acute myeloid leukemia (AML) it is important to elucidate the biological events that lead from remission to relapse, which have a high probability of leading to an adverse disease outcome. 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 “stem-like” 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 “stem-like” cells survive cancer treatment that eradicates other malignant cell clones. This fact differentiates AML “stem-like” 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.https://www.mdpi.com/2073-4409/14/13/1038acute myeloid leukemialeukemia stem cellsstem-like cellsrelapsereactive oxygen speciesaldehyde dehydrogenase
spellingShingle Régis Costello
Garrett M. Dancik
Anaïs Dubiau
Lamia Madaci
Spiros Vlahopoulos
Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
Cells
acute myeloid leukemia
leukemia stem cells
stem-like cells
relapse
reactive oxygen species
aldehyde dehydrogenase
title Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
title_full Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
title_fullStr Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
title_full_unstemmed Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
title_short Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia
title_sort expression of aldehyde dehydrogenase 1a1 in relapse associated cells in acute myeloid leukemia
topic acute myeloid leukemia
leukemia stem cells
stem-like cells
relapse
reactive oxygen species
aldehyde dehydrogenase
url https://www.mdpi.com/2073-4409/14/13/1038
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