Investigating the biology of microRNA links to ALDH1A1 reveals candidates for preclinical testing in acute myeloid leukemia

Abstract

Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is a member of the aldehyde dehydrogenase gene subfamily that encode enzymes with the ability to oxidize retinaldehyde. It was recently shown that high ALDH1A1 RNA abundance correlates with a poor prognosis in acute myeloid leukemia (AML). AML is a hematopoietic malignancy associated with high morbidity and mortality rates. Although there are a number of agents that inhibit ALDH activity, it would be crucial to develop methodologies for adjustable genetic interference, which would permit interventions on several oncogenic pathways in parallel. Intervention in multiple oncogenic pathways is theoretically possible with microRNAs (miRNAs or miRs), a class of small non-coding RNAs that have emerged as key regulators of gene expression in AML. A number of miRNAs have shown the ability to interfere with ALDH1A1 gene expression directly in solid tumor cells, and these miRNAs can be evaluated in AML model systems. There are indications that a few of these miRNAs actually do have an association with AML disease course, rendering them a promising target for genetic intervention in AML cells. Contents1. Introduction 2. Biological links between AML, miRNAs and ALDH1A1 3. miRNAs that may be included in the list of miRNAs with the potential to target ALDH1A1 4. miRNAs that can be studied further in model systems for AML preclinical drug development, based on database output 5. Conclusions