CD56 Has a Key Role in Regulating Multiple Myeloma Cell Growth, Treatment Responses

CD56 signaling by cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB1) reduced responses to lenalidomide in patients with multiple myeloma (MM), which indicates that CREB1 inhibition may be an effective treatment for patients with MM that expresses CD56. These findings were recently presented at the American Society of Hematology’s 2021 Annual Meeting.

To investigate the role of CD56 in MM, researchers at The Ohio State University analyzed 569 patients with MM diagnosed between 2005 and 2014 at the university’s Wexner Medical Center. The researchers stratified patients on the basis of their percentage of CD56-expressing clonal MM cells, then evaluated patient outcomes based on this percentage.

As a result, the researchers found that the mean percentage of CD56-expressing clonal MM cells was 27% and that patients with more than 30% CD56-expressing MM clonal cells had worse outcomes than patients with fewer than 30% CD56-expressing MM clonal cells (median overall survival, 9.6 vs. 7.6 yr; p-value = 0.004).

Next, they evaluated the functional role of CD56 in MM by conducting gain-of-function studies in various cell lines and showed that overexpression of CD56 promotes MM growth and viability, but CD56 silencing of some MM cell lines decreases MM growth and increases apoptotic cell death.

Finally, they used short-hairpin RNAs targeting CREB1, ribosomal protein S6 kinase A3 (RSK2), and specific inhibitors of both CREB1 and RSK2 to show that CD56‑positive MM cell lines are more sensitive to CREB1 or RSK2 inhibition than CD56‑negative MM cell lines are. Similarly, patients with high CD56 expression are more sensitive to CREB1 or RSK2 inhibition than patients with low CD56 expression.

According to the researchers, “Our study defines an effective threshold for therapeutic intervention in CD56-expressing MM patients. Moreover, [...] CD56 can be a prognostic and predictive factor of response in MM.”

—Ellen Kurek

Reference:

Cottini F, Rodriguez J, Birmingham M, et al. CD56 has a critical role in regulating multiple myeloma cell growth and response to therapies. Paper presented at: American Society of Hematology’s 2021 Annual Meeting; December 8-14, 2021; Atlanta, Georgia, and Virtual. https://ash.confex.com/ash/2021/webprogram/Paper146370.html