**4. Conclusions**

This study provided the transcriptomic profiles of two leukemia cells (KG1a and HL60) that had different stemness treated by two kinds of iron nanoparticles (FeNPs and PBNPs) that had different ROS regulation capabilities. The results indicated that the expression of many genes was significantly regulated. More genes were regulated by PBNPs than FeNPs. The unique and common genes were determined. The gene signatures were established. The common genes in all treatments were closely related with iron metabolism, antioxidation, lipid metabolism, vesicle traffic, innate immune system, and cytoskeleton. The mineral absorption pathway was most significantly regulated by PBNPs in both cells, whereas the lipid metabolism pathway was most significantly regulated by FeNPs in HL60. This study shed new insights into the cytotoxicity at the gene transcription level of iron nanoparticles that differently regulate ROS in leukemia cells with different stemness. This study demonstrated why the leukemia cell with low stemness is sensitive and with high stemness is resistant to FeNPs as a ROS inducer. This study also suggested the potential resistance of stemness leukemia cells to iron nanoparticles as a ferroptosis inducer.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2079-4991/10/10/1951/s1, Table S1. The qPCR primers sequences used in this study; Table S2. Mapping statistics of RNA-Seq (each sample had two biological replicates); Table S3. The mRNA peak insert size in all samples; Figure S1. Statistics of the distribution of reads in different regions of the genome; Figure S2. Correlation analysis of gene expression in 12 samples; Figure S3. Density map of gene expression levels of all samples; Figure S4. KEGG analysis of the HIF-1 signaling pathway in Pathview; Figure S5. KEGG analysis of the mineral absorption pathway in Pathview; File S1. DEGs; File S2. GO terms; File S3. KEGG pathways; File S4. Redox-related DEGs.

**Author Contributions:** J.W. conceived the study and designed the experiments. T.L. performed data analysis, qPCR detection, and wrote the manuscript. J.G. performed wet experiments of RNA-Seq. N.L. provided support in data analysis. J.W. edited the manuscript with support from all authors. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the National Key Research and Development Program of China (2017YFA0205502) and the National Natural Science Foundation of China (61971122).

**Conflicts of Interest:** The authors declare no conflict of interest.
