Emerging roles of RNA m6A modification in multiple myeloma pathogenesis and treatment resistance (Review)

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Despite advances in therapeutic agents, including proteasome inhibitors, immunomodulatory drugs and immunotherapies, relapse driven by treatment resistance remains a major clinical challenge. This underscores the critical need to elucidate additional molecular mechanisms that drive MM pathogenesis and therapeutic failure. The emerging field of epitranscriptomics, which studies post‑transcriptional RNA modifications, offers a promising perspective. Among these modifications, N6‑methyladenosine (m⁶A), the most abundant internal mRNA modification, has been implicated in regulating nearly every aspect of RNA metabolism. Growing evidence indicates that dysregulation of the m⁶A modification machinery plays a pivotal role in MM heterogeneity, disease progression and drug resistance. The present review synthesized current knowledge on how specific m⁶A regulators contribute to MM oncogenesis by modulating key signaling pathways, interactions with the bone marrow microenvironment and responses to therapy. It also discussed the potential of targeting m⁶A pathways as a therapeutic strategy to overcome treatment resistance and improve patient outcomes. By highlighting recent advances and future directions, the present review underscored m⁶A modification as an important frontier in the battle against MM.