The Notch1-jagg1 pathway is activated due to MM cell-BMSC adhesion inducing CAM-DR. Inhibition of Notch signaling by GSI (Γ-secretase inhibitor) induces MM cells apoptosis through upregulation of Noxa. Dll1 /Notch pathway also promotes MM cells resistance to bortezomib through upregulation of of CYP1A1, a Cytochrome P450 enzyme. Latter pathway is also constitutively activated in MMCSCs (CD138- cells) which show more resistance to drugs than CD138+ cells through upregulation of BCL-2, MCL-1 and BCL-XL. Notch pathway may contribute to MMDR through MM cells-osteoclast interaction. This evidence concerns the gene BCL2 and Miyoshi myopathy.