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

Abstract

Chronic myeloid leukaemia (CML) is the first clonal myeloproliferative disorder of pluripotent stem cells to be associated with a specific genetic abnormality, the Philadelphia chromosome, bearing the BCR-ABL1 fusion oncogene. Tyrosine kinase inhibitors are used as first-line treatment for the chronic phase of CML, although alternative treatments are necessary for resistant cases. Cannabidiol (CBD) is a major constituent of hemp oil that exerts a broad range of pharmacological effects in various malignancies. However, its molecular mechanisms in leukaemia remain unclear.

In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 μM) for 4 and 12 h, followed by RNA sequencing to identify differentially expressed genes (DEGs). The subsequent transcriptomic profiling revealed 3518 DEGs at 12 h and 3433 DEGs at 4 h of treatment, including significant modulation of metallothionein-regulated oxidative stress responses (MT1, MT2, and SLC30A2) and p53-mediated apoptosis (TP53TG3, DDIT4, BBC3, CHAC1, NOXA1, and DAPK2). Additionally, the DEGs were enriched in alterations in immune signalling pathways—including type I interferon activation and PI3K-Akt-mTOR and Toll-like receptor signalling—crucial in leukaemia progression, as well as variations in lipid metabolism and mitochondrial homeostasis.

The results presented in this study validate the considerable potential of CBD to induce broad transcriptional and signalling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide novel insights into the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in haematological malignancies.

Keywords

Myeloid leukaemia / Cannabidiol / Transcriptome / Metallothioneins

Author contributions

PPD prepared the research proposal of this study. PPD conceptualized and developed the study and experimental framework. PPD conducted all of the experiments and performed data analysis. PPD wrote and refined the paper. STD revised the manuscript.

Data sharing

All sequencing data supporting the findings of this study are publicly available in the NCBI Gene Expression Omnibus (GEO) under accession number GSE305108.

Funding

This study was funded through a grant from the national program “Young Scientists and Post-Doctoral Fellows-2”, Bulgarian Academy of Science.

Conflict of Interest

The author declares no conflict of interest.

Acknowledgments

The author expresses his gratitude for the financial support provided by the Bulgarian National Science Fund under grand number KP-06-M61/6, which contributed to the completion of this study.

The author thanks the Department of Immunology, laboratory of Experimental immunotherapy, as well as department of General Microbiology, laboratory of Microbial genetics at Stephan Angeloff Institute of Microbiology (Bulgarian Academy of Science), for accommodating this research.

The author extends his gratitude to Assoc. Prof. Petya Dimitrova, PhD and Assoc. Prof. Anastas Pashov, MD, PhD for their support.

Appendix A. Supplementary material

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.gmg.2025.100076.

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