Bone marrow mesenchymal stem cells regulate stemness of multiple myeloma cell lines via BTK signaling pathway

Bone marrow mesenchymal stem cells (BM-MSCs) are key components of bone marrow microenvironment. Although the importances of BM-MSCs activation in myeloma cells growth, development, progression, angiogenesis are well known, their role in the regulation of myeloma stemness is unclear. In this study, myeloma cell lines (LP-1, U266) were co-cultured with BM-MSCs, we found that BM-MSCs could up-regulate the expression of key stemness genes and proteins (OCT4, SOX2, NANOG) and increase clonogenicity. Similarly, the mechanisms underlying the BM-MSC activation of myeloma stemness remain unclear. Here, we found that PCI-32765, a Bruton tyrosine kinase (BTK) inhibitor, treatment significantly down- regulate expression of key stemness genes and proteins in vitro co-culture system. Together, our results revealed that BM-MSCs could increase myeloma stemness via activation of the BTK signal pathway.