Related Experiment Video
Updated: Jun 4, 2025
A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
ALDH Enzymes and Hematological Diseases: A Scoping Review of Literature
Amélie Foucault1,2, Olivier Hérault1,2,3,4,5
1Department of Biological Hematology, Tours University Hospital, 37000 Tours, France.
Insights
Aldehyde dehydrogenases (ALDHs) are enzymes crucial for detoxification and stem cell identification. ALDH2, in particular, impacts hematopoiesis and is linked to various blood disorders, presenting potential as a biomarker and therapeutic target.
Area of Science:
- Biochemistry and Molecular Biology
- Hematology
- Cancer Stem Cell Research
Background:
- Aldehyde dehydrogenases (ALDHs) are a superfamily of enzymes critical for metabolizing aldehydes, playing vital roles in physiological and toxicological processes.
- ALDHs are recognized as significant markers for identifying and quantifying hematopoietic stem cells and cancer stem cells, including leukemic stem cells.
- ALDH2 is a key isoenzyme involved in detoxifying toxic aldehydes like acetaldehyde and formaldehyde, essential for normal hematopoiesis.
Purpose of the Study:
- To review the current understanding of ALDH family members and their roles in normal and malignant hematopoiesis.
- To highlight the specific involvement of the ALDH2 isoenzyme in congenital and acquired hematological diseases.
- To explore the potential of ALDHs as biomarkers and therapeutic targets for identifying and eradicating leukemic stem cells.
Main Methods:
- Literature review of existing studies on ALDH enzymes and their functions in hematopoiesis.
- Analysis of ALDH2's role in aldehyde detoxification and its association with hematological malignancies.
- Examination of the ALDH2*2 variant allele's prevalence and its link to hematological diseases.
Main Results:
- ALDHs, particularly ALDH2, are integral to aldehyde detoxification, influencing hematopoietic stem cell function and differentiation.
- The ALDH2*2 variant is prevalent in East Asian populations and is associated with altered acetaldehyde metabolism and increased risk of hematological diseases.
- ALDH2 plays a critical role in preventing formaldehyde accumulation during hematopoietic progenitor differentiation, ensuring normal blood cell formation.
Conclusions:
- ALDH enzymes, especially ALDH2, are crucial for maintaining normal hematopoiesis and are implicated in various congenital and acquired blood disorders.
- ALDH2's function in detoxifying aldehydes makes it a potential biomarker for diagnosing and monitoring hematological diseases.
- Targeting ALDHs offers a promising therapeutic strategy for eradicating cancer stem cells in hematological malignancies.
Abstract:
Aldehyde dehydrogenases (ALDHs) constitute a group of enzymes that catalyze the oxidation of aldehydes to carboxylic acids. The human ALDH superfamily, including 19 different isoenzymes (ALDH1A1, ALDH1A2, ALDH1A3, AHDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1, ALDH9A1, ALDHA16A1, ALDH18A1), displays different key physiological and toxicological functions, with specific tissue expression and substrate specificity. Several studies have established that ALDH are interesting markers for the identification and quantification of human hematopoietic stem cells and cancer stem cells, notably leukemic stem cells. ALDH2 is the best-documented enzyme, in this family, as having an impact on hematology, particularly myeloid malignancies. ALDH2 mainly catalyzes the detoxification of toxic aldehydes (acetaldehyde, formaldehyde). For example, ALDH2 detoxifies formaldehyde, which is produced during the differentiation of hematopoietic progenitors. The trigger of alcohol dehydrogenase 5 (also known as formaldehyde dehydrogenase or S-nitrosoglutathione reductase, ADH5/FDH/GSNOR)/ALDH2 allows to eliminate formaldehyde and ensures normal hematopoiesis. Moreover, the ALDH2*2 variant allele is the most frequent ALDH2 variant, found in 35-45% of individuals of East Asian origin. It is associated with altered acetaldehyde metabolism and is involved in several hematological diseases (aplastic anemia, bone marrow failure, myelodysplastic syndrome). This review presents current knowledge of different members of the ALDH family and their involvement in normal and malignant hematopoiesis. Focus was brought to the ALDH2 isoenzyme in congenital (Fanconi anemia, Aplastic anemia, mental retardation, and dwarfism (AMeD) syndrome, and idiopathic aplastic anemia) and acquired (acute myeloid leukemia and myelodysplastic syndrome) hematological diseases. It also describes the possibilities of using ALDH as both a biomarker and therapeutic target, to identify and eradicate leukemic stem cells in malignant diseases.
Related Concept Videos
01:21Hematopoiesis
01:01Regulation of Hematopoietic Stem Cells
01:15Blood Transfusion
Blood Transfusion Overview
A blood transfusion is a medical procedure used to replace blood lost due to injury, surgery, or to treat conditions such as anemia or cancer. During a transfusion, donor blood is...
01:20Overview of Hematopoiesis
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
01:27Disorders of Erythrocytes
Erythrocyte disorders can be broadly categorized into two main types: anemic and polycythemic conditions.
A low oxygen-carrying capacity of the blood due to the loss, lower production, or destruction of erythrocytes is termed anemia. Hemorrhagic anemia, for example, occurs when bleeding from an external wound or internal ulcer reduces erythrocyte counts.
On the other...
02:45Blood Transfusion and Agglutination
History
The history of blood transfusion dates back to the 17th century, when early attempts were made in animals. In 1818 James Blundell, a British doctor, performed the first successful human blood transfusion. Later in 1900, Karl...