The clinical relevance of these findings stems from the following evidences: 1) Notch activity (assessed as HES6 gene expression) and RANKL expression are directly correlated in primary MM cells and in the differently osteoclastogenic MM cells lines (U266 and OPM2) used in this work; 2) the inhibition of Notch signaling hampers the pro-osteoclastogenic potential of primary MM cells; 3) RANKL expression in MM cells correlates with osteolytic bone disease [42, 43], and, accordingly, 4) RANKL targeting has been reported to prevent myeloma bone disease [44]. The gene discussed is TNFSF11; the disease is Miyoshi myopathy.