Bioinformatics differential expression analysis of the effect of cannabidiol in chronic myeloid leukemia cell line

Chronic myeloid leukemia (CML) is the first clonal myeloproliferative disorder of the pluripotent stem cell to be associated with a specific genetic abnormality, the Philadelphia chromosome, bearing the BCR-ABL1 fusion oncogene. First treatment option for control of the chronic phase of CML are the tyrosine kinase inhibitors (TKIs), though alternative treatments are necessary for resistant cases. Cannabidiol (CBD), one of the major constituents of hemp oil exerts a broad range of pharmacological effects in various malignancies, yet its molecular mechanisms in leukemia remain unclear. In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 µM) for 4 and 12 hours, followed by RNA sequencing to identify differentially expressed genes (DEGs). The consecutive transcriptomic profiling revealed 3518 DEGs at 12 hours and 3433 DEGs at 4 hours of treatment, showing significant modulation of metallothionein-regulated oxidative stress responses (MT1, MT2, SLC30A2), p53-mediated apoptosis (TP53TG3, DDIT4, BBC3, CHAC1, NOXA1, DAPK2), alteration in immune signaling pathways, including type I interferon activation, PI3K-Akt-mTOR and Toll-like receptor signaling, crucial in leukemia progression, as well as shifts in lipid metabolism and mitochondrial homeostasis. The results presented in this study invigorate the considerable potential of CBD to induce broad transcriptional and signaling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide new insights in the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in hematological malignancies. Overall design: RNA-seq profiling was performed on wild-type K562 cells under three conditions: untreated control, treatment with cannabidiol (CBD) for 4 hours, and treatment with CBD for 12 hours.