CBD triggered broad gene expression changes in leukemia cells affecting immune, stress, and cell death pathways

CBD treatment at its IC50 (17.69 microM) induced 3,518 DEGs at 12 hours and 3,433 at 4 hours. Key changes included upregulation of metallothionein-regulated oxidative stress responses (MT1, MT2, SLC30A2) and p53-mediated apoptosis genes (TP53TG3, DDIT4, BBC3, CHAC1, NOXA1, DAPK2). Pathway enrichment identified type I interferon activation, PI3K-Akt-mTOR signaling, Toll-like receptor signaling, and alterations in lipid metabolism and mitochondrial homeostasis.

Imatinib-sensitive K-562S chronic myeloid leukemia cells were treated with CBD at its IC50 concentration (17.69 microM) for 4 and 12 hours. RNA sequencing was performed, and differentially expressed genes were identified and analyzed through pathway enrichment analysis.

Chronic myeloid leukemia treated with tyrosine kinase inhibitors like imatinib can develop resistance. Understanding how CBD affects leukemia cells at the molecular level could identify complementary pathways to overcome resistance or enhance treatment effects.

The breadth of transcriptional changes (over 3,400 genes) suggests CBD has far-reaching effects on leukemia cell biology rather than acting through a single pathway. The convergence on immune modulation, apoptosis, and metabolic processes aligns with known cannabinoid biology but provides the first detailed transcriptomic map in CML cells.

In vitro study in a single cell line (K-562S), which may not represent the heterogeneity of CML in patients. Only imatinib-sensitive cells were tested. The CBD concentration (IC50) may not be achievable in patient plasma. Transcriptomic changes do not necessarily translate to protein-level or functional effects.