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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Wednesday, August 3, 2022
Inhibition of the neural cell adhesion molecule CD56 may be a novel therapeutic target to improve clinical outcomes for patients with multiple myeloma, according to Francesca Cottini, MD, of The Ohio State University, Columbus, and colleagues. CD56 overexpression was found to be associated with increased myeloma cellular growth and adhesion as well as reduced prognosis and response to autologous stem cell transplantation (ASCT). The findings of this study were published in the journal Molecular Cancer Research.
“CD56 signaling promotes multiple myeloma growth and adhesion, by activating CREB1 target genes, MCL1 and BCL2. Inhibition of CREB1 alone or in combination with lenalidomide is an unexplored synthetic lethal approach in CD56-expressing patients with multiple myeloma,” stated the study authors.
Multiple myeloma cell lines and bone marrow aspirates were obtained, and CD56-expressing CD138-positive, light-chain–restricted multiple myeloma cells were identified through immunophenotyping. Cellular growth, apoptosis, and gene expression were then identified within these samples. The Kaplan-Meier method was used to identify associations between CD56 levels and the clinical prognosis in patients’ medical records.
Samples with more than 10% of CD56-expressing clonal multiple myeloma cells were associated with reductions in the rates of overall survival, responses to immunomodulatory drugs, ASCT, and lenalidomide maintenance. Additionally, the clone size of CD56-expressing multiple myeloma cells was increased in the majority of cases with disease progression. Patients with high expression of MMSET/NSD2 or the presence of t(4;14) had higher levels of CD56 or bigger CD56 clone size. Cells that overexpressed CD56 also had low levels of the target protein for lenalidomide, CRBN. Inhibition of CREB1/RSK2 within these cells rescued CRBN and led to lenalidomide-induced cellular lethality, according to the study authors. In addition, CD56 altered the ratio of the antiapoptotic genes BCL2/MCl1, which was associated with decreased responsivity to venetoclax.
The authors concluded: “We believe our study paves the way for using the CD56 clone size as a predictive marker of response to lenalidomide and possibly venetoclax therapy.”
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
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