Multiple Myeloma Develops Differently in Men and Women

Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have uncovered biological differences in how multiple myeloma develops and progresses in men and in women. The rare blood cancer occurs more often in men than in women, making these biological differences important for understanding why multiple myeloma affects the sexes differently.

Their findings, recently published in Blood Cancer Journal and led by Reza Shahbazi, PhD, provide new knowledge that could lead to earlier detection and more targeted, sex-specific treatment strategies. Shahbazi is an assistant professor of medicine at the IU School of Medicine and a researcher at the cancer center and its Brown Center for Immunotherapy.

"The same therapies are provided for men and women facing multiple myeloma, but we know men develop the disease more often," Shahbazi said. "In our research, we found there are key non-coding RNAs that differ between men and women. Those specific targets could help us develop personalized therapies or choose the best therapies for individual patients."

The study was done in collaboration with the Mayo Clinic using multiple myeloma cells from bone marrow aspirates from 24 Mayo patients. Researchers also used multiple myeloma cell lines developed by researchers at IU and Mayo.

Shahbazi's lab used these cells to examine differences between the sexes at the molecular level. The researchers found that the non-coding RNA inside exosomes — small particles released by cells that carry messages between cells — varied between male and female patients.  By analyzing exosomes, which circulate throughout the body and therefore provide a more sensitive readout of disease biology, rather than whole bone marrow tissue, the team was able to detect molecular differences often missed by standard approaches.

"Non-coding RNAs end up packaged inside the exosomes to be sent out for a cellular response — so they get packaged inside the cells, and in this case, multiple myeloma cells," Shahbazi said. "We identified that the exosomes from the male and female patients are totally different, despite commonalities. They carry specific messages that could help us with the diagnosis of the disease. Many of these non-coding RNAs regulate genes involved in immune response, cell growth and drug resistance, making them potential biomarkers."

Early detection is critical for successful treatment of multiple myeloma, and Shahbazi believes these markers could eventually help clinicians diagnose the disease sooner and better predict disease severity and responses to therapy.

The next step for the research team is to validate the findings in a larger patient cohort using IU resources.

Reference: Maleknia S, Rezaei Benam S, Ahmann G, Fonseca R, Jelinek DF, Shahbazi R. Sex-specific dysregulation of exosomal non-coding RNAs drives multiple myeloma progression. Blood Cancer J. 2025;15(1):162. doi: 10.1038/s41408-025-01362-1

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