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Potential Immunogenic Cell Death–Related Predictor of Therapeutic Response in Myeloma

By: Julia Fiederlein Cipriano, MS
Posted: Thursday, August 24, 2023

According to Yunfeng Fu, MD, of the Third Xiangya Hospital of Central South University, Changsha, China, and colleagues, interleukin-5 receptor subunit alpha (IL5RA) is highly expressed in multiple myeloma and high-risk smoldering multiple myeloma. Their findings, which were published in the journal Scientific Reports, also highlighted the potential involvement of this apparent immunogenic cell death–related regulator in cell signal transduction, immune infiltration, immune checkpoints, and N6-methyladenosine mRNA modification in multiple myeloma.

“Our study reveals the landscape of immunogenic cell death expression and the potential regulatory significance of IL5RA on immunogenic cell death in multiple myeloma,” the investigators commented. “IL5RA may be a potential immunogenic cell death–related predictor for therapeutic response in multiple myeloma.”

Using the Gene Expression Omnibus database, the investigators analyzed the microarray data from multiple myeloma (n = 45), smoldering multiple myeloma (progressed: n = 10; nonprogressed: n = 12), and control (n = 3) samples. IL5RA was found to be upregulated in myeloma and progressed smoldering myeloma. The investigators reported enrichment in pathways such as the PI3K-Akt signaling pathway, as well as natural killer cell–mediated cytotoxicity, in the samples with high IL5RA expression levels. IL5RA seemed to be associated with secretory protein genes such as CST6.

Enrichment of cellular apoptosis and the Hippo signaling pathway was observed in differential genes of the immunogenic cell death cluster. Furthermore, IL5RA appeared to be associated with immune infiltration, immunogenic cell death–related genes, immune checkpoint–related genes, and N6-methyladenosine mRNA in myeloma. Based on in vitro and in vivo experiments, IL5RA is involved in apoptosis, proliferation, and drug resistance of myeloma cells.

Disclosure: The study authors reported no conflicts of interest.

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