A study published in Global Medical Genetics by researchers at the Stephan Angeloff Institute of Microbiology has found that cannabidiol (CBD) produces wide-ranging genetic and molecular effects in chronic myeloid leukemia (CML) cells, suggesting therapeutic potential for resistant cases of the disease.

CML, a blood cancer characterized by the Philadelphia chromosome and the BCR-ABL1 fusion oncogene, is typically treated with tyrosine kinase inhibitors. However, resistance to these drugs creates an urgent need for alternative strategies. In this study, imatinib-sensitive K-562S cells were exposed to CBD, which inhibited cell proliferation in a dose-dependent manner, with an IC50 of 17.69 μM.

RNA sequencing at 4 and 12 hours revealed thousands of differentially expressed genes. Among the most notable were metallothioneins (MT1 and MT2), which regulate oxidative stress and metal ion homeostasis, and p53-linked apoptotic mediators such as TP53TG3, BBC3 (PUMA), DDIT4, CHAC1, and DAPK2. These changes indicated that CBD triggered stress-induced apoptosis.

The analysis also uncovered enrichment in immune-related pathways, including type I interferon activation, PI3K-Akt-mTOR, Toll-like receptor signaling, and complement system activity. Several genes involved in viral mimicry and immune surveillance, such as PDCD1 and IFIT1, were also affected. Additionally, CBD modulated lipid metabolism and mitochondrial processes, pointing to broader metabolic disruption in leukemia cells.

Pathway analysis confirmed CBD’s influence on zinc and copper homeostasis, fatty acid transport, apoptosis networks, and immune signaling. Researchers concluded that CBD initiates a two-phase response: an early activation of metal detoxification and stress responses, followed by suppression of gene expression programs linked to survival and proliferation.

These findings highlight CBD’s capacity to alter transcriptional regulation, immune pathways, and apoptosis in leukemia cells, reinforcing its potential role as an anticancer agent. The authors suggest that future studies should explore CBD’s use in combination therapies and its precision applications in hematological malignancies.