Purpose: The role of Exosomal RNAs in the bone marrow microenvironment and their prognostic significance in multiple myeloma is not fully understood, especially in physically active populations such as athletes. This study aims to evaluate specific exosomal RNAs, including hsa-miR-124-3p, as potential prognostic markers for multiple myeloma in athletes.

Experimental Design: Bone marrow fluid was collected from athletes diagnosed with multiple myeloma, showing varying treatment responses. Exosomes were isolated and characterized through dynamic light scattering, transmission electron microscopy, and Western blot analysis. The effect of these exosomes on PRMI8226 cell migration and proliferation was observed. MiRNA sequencing of the exosomes was performed, followed by bioinformatics analysis to identify differentially expressed miRNAs related to treatment outcomes. Clinical sample validation was conducted to ascertain the relevance of these findings in a broader athletic context.

Results: The study revealed that bone marrow-derived exosomes from athletes with multiple myeloma exhibit varied impacts on PRMI8226 cells based on the therapeutic response. Exosomes associated with poor prognosis were found to enhance PRMI8226 cell proliferation and migration. MiRNA sequencing identified distinct miRNA expressions in exosomes, with certain miRNAs enriched in cancer-related pathways. Notably, exosomal hsa-miR-124-3p was highly expressed in athletes exhibiting poor therapeutic responses.

Conclusion: This study highlights the crucial role of exosomal miRNA in the progression and treatment of multiple myeloma in athletes. Specific miRNAs, such as hsa-miR-124-3p, hsa-miR-451b, and hsa-miR-509-3p, were predominantly expressed in athletes with less favorable treatment outcomes. Among these, hsa-miR-124-3p shows significant potential as a prognostic marker for therapeutic efficacy in athletes, providing a new avenue for early detection and management of multiple myeloma in this specific population.