Cellular Iron Status Is Associated With Better Survival And Increased Chemotherapy Sensitivity In Aml

Iron is mainly used in oxygen transfer reactions including reactions necessary for cellular proliferation. Since iron is essential for cellular processes, but excess iron is toxic, complex pathways have evolved to maintain iron homeostasis in various subcellular compartments. Genomic studies by others of samples in a breast cancer tissue bank have indicated that mRNA expression of iron regulatory genes predicting low iron cellular import and high iron cellular export are associated with a good prognosis, indicating that lower bioavailable cellular iron is associated with slower tumor growth rate and better patient survival. Our genomic analysis of 168 de novo AML samples reported in The Cancer Genome Atlas (TCGA) study however showed an opposite result to the breast cancer studies: 1) High iron uptake indicated by high transferrin receptor mRNA and low HFE mRNA, 2) Increased intracellular labile iron (bioavailable iron) indicated by low ferritin heavy chain to light chain ratio and 3) Less iron efflux indicated by low ferroportin; were all associated with significantly increased survival (p in vivo with a single recommended IV iron dose commonly used for iron deficiency) significantly increased the growth inhibitory effect of Idarubicin (IDA) or Cytarabine (Ara-C). Growth inhibition by Ara-C or IDR was significantly increased with added iron in single experiments and was consistent; for example three consecutive experiments on separate days using MOLM-13 treated with Ara-C (1uM) or IDR (30 nM), added Fe showed significantly increased inhibition of proliferation at 24h (paired t p Disclosures No relevant conflicts of interest to declare.