We recently demonstrated that variable levels of CXCR4 are present on cell surfaces of different subpopulations of MM cells and that cell surface levels of CXCR4 highly correlate with BTK expression in primary MM cells.16 Expression of BTK is higher in MM cells adherent to fibronectin or to stromal cells than in nonadherent cells.17,33 The current work showed that the levels of CXCR4 and BTK were relatively lower in MM cells residing within focal lesions than in those within interstitial marrow and in primary MM cells after coculture with osteoclasts. This evidence concerns the gene CXCR4 and Miyoshi myopathy.