Lower RNA expression of ALDH1A1 distinguishes the favorable risk group in acute myeloid leukemia

Abstract

AbstractThe expression and activity of enzymes that belong to the aldehyde dehydrogenases is a characteristic of both normal and malignant stem cells. ALDH1A1 is an enzyme critical in cancer stem cells. In acute myeloid leukemia (AML), ALDH1A1 protects leukemia-initiating cells from a number of antineoplastic agents, which include inhibitors of protein tyrosine kinases. Furthermore, ALDH1A1 proves vital for the establishment of human AML xenografts in mice. We review here important studies characterizing the role of ALDH1A1 in AML and its potential as a therapeutic target. We also analyze datasets from leading studies, and show that decreased ALDH1A1 RNA expression consistently characterizes the AML patient risk group with a favorable prognosis, while there is a consistent association of high ALDH1A1 RNA expression with high risk and poor overall survival. Our review and analysis reinforces the notion to employ both novel as well as existing inhibitors of the ALDH1A1 protein against AML.