Genome-Wide Gene Expression Profiling Defines the Mechanism of Anticancer Effect of Colorectal Cancer Cell-Derived Conditioned Medium on Acute Myeloid Leukemia.

Abstract

Acute myeloid leukemia (AML) is the most common type of leukemia in adults, accounting for 30% of all adult leukemia cases. While there have been recent improvements in the prognosis of the disease, the prognosis remains grim, and further understanding of AML and the development of new therapeutic agents is critical. This study aimed to investigate the potential interaction between colorectal cancer (CRC) cells and AML cells. Unexpectedly, we found that CRC cell-derived conditioned medium (CM) showed anticancer activities in AML cells by inducing apoptosis and differentiation. Mechanistic studies suggest that these phenotypes are closely associated with the suppression of PI3K/AKT/mTOR and MAPK survival signaling, the upregulation of myeloid differentiation-promoting transcription factors c/EBPα and PU.1, and the augmentation of executioner caspases-3/7. Importantly, bioinformatic analyses of our gene expression profiling data, including that derived from principal component analysis (PCA), volcano plots, boxplots, heat maps, kyoto encyclopedia of genes and genomes (KEGG) pathways, and receiver operating characteristic (ROC) curves, which evaluate gene expression profiling data, provided deeper insight into the mechanism in which CRC-CM broadly modulates apoptosis-, cell cycle arrest-, and differentiation-related gene expression, such as BMF, PLSCR3, CDKN1C, and ID2, among others, revealing the genes that exert anticancer effects in AML cells at the genomic level. Collectively, our data suggest that it may be worthwhile to isolate and identify the molecules with tumor-suppressive effects in the CM, which may help to improve the prognosis of patients with AML.