Abstract
Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ALDHbr population or CD34+CD38−ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment. However, inconsistent results have been shown for markers of LSCs, which makes it even more difficult to differentiate LSCs and HSCs. In this review, we elevated the role of ALDH to be a potential marker to define and distinguish HSCs and LSCs and its importance in prognosis and target therapy in AML patients. In addition to immunophenotypical markers, ALDH is also functionally active in defining and distinguishing HSCs and LSCs and offers intracellular protections against cytotoxic drugs. Targeting ALDH may be a potential strategy to improve AML treatment. Additional studies concerning specific targeting ALDH and mechanisms of its roles in LSCs are warranted.
Highlights
Acute myeloid leukemia (AML) is a clonal disorder defined by the accumulation of abnormally differentiated myeloid cells, which lead to a series of fetal clinical problems
Mounting evidences showed that AML arises from genetic changes in hematopoietic stem cells (HSCs) or hematopoietic progenitors [2, 3] and is organized as a hierarchy that is maintained by leukemia stem cells (LSCs), which in turn initiates the abnormal differentitation program and leads to the production of terminal blast cells [4, 5]
Another mechanism behind aldehyde dehydrogenase (ALDH) functions is through retinoic acid (RA) signaling, as ALDH1 catalyzes the oxidation of RA, which can drive the transcription of target genes via a heterodimer formed by RA receptors (RAR) and retinoid-X-receptor [24]
Summary
Acute myeloid leukemia (AML) is a clonal disorder defined by the accumulation of abnormally differentiated myeloid cells, which lead to a series of fetal clinical problems. They are heterogeneous in morphologic and cytogenetic features, and their prognoses are extremely different and individualized. A variety of new trials, including targeted immune therapy, have been developed and tested in clinical practice, but each of these concepts has its particular merits and inherent problems, and none of them have changed the outcome of AML significantly [1]. BioMed Research International immunophenotypical surface markers are not reliable to define LSCs. ALDH is proved to be an interesting candidate both in normal HSCs and in leukemia transformation
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