By: Kerri Fitzgerald
A mouse model confirmed the aggressive nature of CD38 expression in multiple myeloma (MM), which induces widespread metastasis, extensive bone degradation, renal involvement, and heightened immunosuppression. The study was presented at the American Association for Cancer Research Annual Meeting 2025 held in Chicago.
The researchers used CRISPR/Cas9 gene editing via a CD38 knock-out clone of a human MM cell line that was xenografted into immunodeficient mice. Three groups of mice were assessed:
- Human MM with CD38 expression
- Human MM without CD38 expression
- Tumor-naïve control group
The mice were then monitored via bioluminescence imaging (BLI), blood analysis, and PET/CT scans to assess tumor burden.
Compared with the nonmutated genes, BLI showed a significantly increased tumor burden in the CD38 knock-out MM mice at four weeks; these mice also had significantly decreased bone density, with altered levels of IL-6 and RANKL. Blood analysis indicated elevated markers of disease progression and renal dysfunction, with reduced leukocyte and thrombocyte production in the knock-out MM mice.
“These results showcase the critical importance of CD38 expression levels and suggest a potential role for CD38 and related transcriptional changes in contributing to the aggressive phenotype of MM,” the authors concluded.
Reference
Dyer R, Zheleznyak A, Teubnar E, et al. Depleting CD38 leads to an aggressive phenotype of multiple myeloma. Abstract #64. Presented at the American Association for Cancer Research Annual Meeting 2025; April 25-30, 2025; Chicago, IL.
