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The Systemic Cytokine Environment Is Permanently Altered in Multiple Myeloma

Figure 5

A model of possible regulation of MM-CSC by IL-3/GM-SCF and IL-7.

Based on our observation that MM, but not normal, plasma supported the growth of the MM clone and maintained dormancy of MM-CSC [30], we speculate that IL-3 and GM-CSF induce differentiation of MM-CSC (unpublished), and have to be downregulated in patients to prevent the loss of the MM-CSC due to differentiation, and thus, contribute to maintaining the pool of MM-CSCs that can be activated to initiate a relapse. Conversely, since IL-7 stimulates proliferation of the B cells, its expression has to be maintained at higher levels to ensure that the B cell population of the multiple myeloma clone, and thus, the MM-CSC, persists through treatment and remission.

Figure 5