The role of Notch signaling in multiple myeloma

The bone marrow (BM) microenvironment plays a critical role in the multiple myeloma (MM) cell growth and survival. As a highly conserved cell signaling system, the Notch pathway is considered to regulate cell fate determination, stem cell self-renewal, proliferation and apoptosis. Notch receptors and ligands are expressed both in MM cells and the BM microenvironment. In this review, we mainly discuss the canonical Notch signaling pathway including background and components of the signaling, its activation, the downstream targets, its regulation and crosstalk with other pathways. We further focus on the role of Notch signaling in multiple myeloma cell growth, angiogenesis, differentiation, drug resistance, bone disease, metastasis and stem cell biology. A better understanding of Notch signaling in myeloma may provide new strategies to improve current treatment and overall survival.