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Aldehyde Dehydrogenase Genes as Prospective Actionable Targets in Acute Myeloid Leukemia
Garrett M Dancik1, Lokman Varisli2, Veysel Tolan2
1Department of Computer Science, Eastern Connecticut State University, Willimantic, CT 06226, USA.
Insights
Aldehyde dehydrogenase (ALDH) family genes ALDH1A1 and ALDH2 are key targets for improving acute myeloid leukemia (AML) treatment. Inhibiting both ALDH1A1 and ALDH2 shows promise for treating high-risk AML patients.
Area of Science:
- Biochemistry
- Oncology
- Bioinformatics
Background:
- Aldehyde dehydrogenase (ALDH) family member ALDH1A1 is associated with acute myeloid leukemia (AML) risk.
- Previous research on specific ALDH genes in AML has been limited by functional redundancy within the ALDH family.
- Targeting ALDH1A1 expression in AML cells can enhance chemotherapy effectiveness.
Purpose of the Study:
- To evaluate all nineteen ALDH family genes as potential therapeutic targets for AML treatment.
- To investigate the specific roles of ALDH1A1 and ALDH2 in AML patient risk classification and survival.
- To identify actionable targets for improving AML treatment strategies.
Main Methods:
- Bioinformatics evaluation of all nineteen ALDH family genes.
- Analysis of the association between ALDH gene expression and AML patient risk group classification.
- Assessment of the correlation between ALDH gene expression and AML patient survival rates.
Main Results:
- ALDH1A1 is implicated in the development of recurrent AML.
- ALDH1A1 and ALDH2 show the strongest association with AML patient risk group classification among all ALDH family members.
- Combined expression of ALDH1A1 and ALDH2 correlates more strongly with AML risk classification and survival than individual genes.
Conclusions:
- ALDH1A1 and ALDH2 are identified as promising actionable targets for AML treatment, particularly in high-risk patients.
- Inhibitors targeting the enzymatic activities of both ALDH1A1 and ALDH2 represent potential therapeutic agents for AML.
- Further research into dual ALDH1A1 and ALDH2 inhibitors could lead to improved AML treatment outcomes.
Abstract:
It has been previously shown that the aldehyde dehydrogenase (ALDH) family member ALDH1A1 has a significant association with acute myeloid leukemia (AML) patient risk group classification and that AML cells lacking ALDH1A1 expression can be readily killed via chemotherapy. In the past, however, a redundancy between the activities of subgroup members of the ALDH family has hampered the search for conclusive evidence to address the role of specific ALDH genes. Here, we describe the bioinformatics evaluation of all nineteen member genes of the ALDH family as prospective actionable targets for the development of methods aimed to improve AML treatment. We implicate ALDH1A1 in the development of recurrent AML, and we show that from the nineteen members of the ALDH family, ALDH1A1 and ALDH2 have the strongest association with AML patient risk group classification. Furthermore, we discover that the sum of the expression values for RNA from the genes, ALDH1A1 and ALDH2, has a stronger association with AML patient risk group classification and survival than either one gene alone does. In conclusion, we identify ALDH1A1 and ALDH2 as prospective actionable targets for the treatment of AML in high-risk patients. Substances that inhibit both enzymatic activities constitute potentially effective pharmaceutics.
