Study: CBD May Help Overcome Leukemia Drug Resistance by Targeting microRNAs

A new lab study published in the journal Global Medical Genetics reports that cannabidiol (CBD) could help counter resistance to a key leukemia drug by reshaping tiny genetic regulators carried in exosomes. Researchers from the Bulgarian Academy of Sciences and Sofia University St. Kliment Ohridski focused on chronic myelogenous leukemia (CML), a blood cancer driven by the BCR-ABL1 fusion oncogene. For years, tyrosine kinase inhibitors like Imatinib mesylate have transformed CML from a once-deadly diagnosis into a largely manageable condition, but resistance to these drugs remains a serious challenge for many patients.

To explore whether CBD might influence drug sensitivity, the team analyzed exosomal microRNA (miRNA) profiles in two CML cell lines: one Imatinib-sensitive (K-562S) and one Imatinib-resistant (K-562R). Cells were treated with CBD alone, Imatinib alone, or a combination of CBD and Imatinib, and the researchers then examined how exosomal miRNAs shifted in response. They also used Gene Ontology enrichment and semantic clustering to map out the biological pathways affected.

In Imatinib-sensitive K-562S cells, CBD triggered a pattern of tumor-suppressive and apoptosis-related miRNAs, supporting its antiproliferative and pro-apoptotic reputation from other cancer models. In contrast, the resistant K-562R cells displayed a mixed reaction, with changes involving oncogenic miRNAs and regulators of cellular metabolism, suggesting a more complex tug-of-war between survival and cell death pathways.

Imatinib alone produced the expected suppressive signaling cascades in sensitive cells, but in resistant cells it was associated with a loss of canonical tumor suppressor signals. When CBD and Imatinib were combined, the effects diverged sharply between the two models: sensitive cells showed a synergistic boost in apoptosis and differentiation-related pathways, while resistant cells showed only partial restoration of apoptotic control and a continued loss of some tumor suppressor activity.

A key part of the analysis centered on miRNAs linked to HMGB1, a protein involved in cell stress and inflammation that has been connected to cancer progression and therapy resistance. Among the HMGB1-associated miRNAs, the study found suppression of miR-615-5p, miR-4435, let-7g-3p, and members of the miR-548 family, alongside increased levels of miR-3191-3p and miR-33a-5p. These shifts, the authors note, could help explain how CBD and Imatinib together nudge leukemia cells back toward programmed cell death.

The researchers conclude that circulating miRNAs, especially those tied to HMGB1, are promising biomarkers of tyrosine kinase inhibitor resistance in CML. More importantly, they argue that targeting these miRNAs in combination with CBD and Imatinib could eventually offer a strategy to re-establish apoptotic regulation and counteract resistance mechanisms.

Although the findings are limited to cell-line experiments, the work adds to a growing body of preclinical evidence that CBD can interact with established cancer therapies in ways that may be clinically relevant, and it lays out specific miRNA targets for future animal studies and, potentially, human trials.

The full text of the study can be found here.