CAMKIIγ is a targetable driver of multiple myeloma through CaMKIIγ/ Stat3 axis.

Aberrant activation of CAMKII gamma has been linked to leukemia and T-cell lymphoma, but not multiple myeloma (MM). The purpose of this study was to explore the role of CaMKII gamma in the pathogenesis and therapy of MM. In this study, we found that CaMKII. was aberrantly activated in human MM and its expression level was positively correlated with malignant progression and poor prognosis. Ectopic expression of CaMKII gamma promoted cell growth, colony formation, cell cycle progress and inhibited apoptosis of MM cell lines, whereas, knockdown of CAMKII gamma expression suppressed MM cell growth in vitro and in vivo. Mechanically, we observed that CaMKII gamma overexpression upregulated p-ERK and p-Stat3 levels and suppression of CaMKII gamma had opposite effects. CaMKII gamma is frequently dysregulated in MM and plays a critical role in maintaining MM cell growth through upregulating STAT3 signaling pathway. Furthermore, our preclinical studies suggest that CaMKII gamma is a potential therapeutic target in MM, and could be intervened pharmacologically by small-molecule berbamine analogues.