SPHK1 and Miyoshi myopathy: To further confirm the role of intracellular S1P in MM cell survival, we investigated if microenvironmental signals, such as adhesive interactions with stromal cells—shown above to induce GFI1-dependent upregulation of P-SphK1 (Figure 3F)—or osteocytes—previously reported to support MM cell proliferation [47]—can prevent SK1-I induced MM cell death.