The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia

The protein family of aldehyde dehydrogenases (ALDH) encompasses nineteen members. The ALDH1 subfamily consists of enzymes with similar activity, having the capacity to neutralize lipid peroxidation products and to generate retinoic acid; however, only ALDH1A1 emerges as a significant risk factor in acute myeloid leukemia. Not only is the gene ALDH1A1 on average significantly overexpressed in the poor prognosis group at the RNA level, but its protein product, ALDH1A1 protects acute myeloid leukemia cells from lipid peroxidation byproducts. This capacity to protect cells can be ascribed to the stability of the enzyme under conditions of oxidant stress. The capacity to protect cells is evident both in vitro, as well as in mouse xenografts of those cells, shielding cells effectively from a number of potent antineoplastic agents. However, the role of ALDH1A1 in acute myeloid leukemia has been unclear in the past due to evidence that normal cells often have higher aldehyde dehydrogenase activity than leukemic cells. This being true, ALDH1A1 RNA expression is significantly associated with poor prognosis. It is hence imperative that ALDH1A1 is methodically targeted, particularly for the acute myeloid leukemia patients of the poor prognosis risk group that overexpress ALDH1A1 RNA.

Automated summary

The ALDH protein family has nineteen members, with ALDH1A1 emerging as a significant risk factor in acute myeloid leukemia. ALDH1A1 is overexpressed in the poor prognosis group at both the RNA and protein levels, protecting leukemia cells from lipid peroxidation byproducts. This protection is due to the enzyme's stability under oxidant stress, and it shields cells effectively in both in vitro and in vivo experiments. Despite normal cells often having higher ALDH activity, ALDH1A1 RNA expression is significantly associated with poor prognosis in acute myeloid leukemia patients, emphasizing the importance of targeting ALDH1A1 in this specific group.