In agreement with this, in normal mouse B-cell development Ikaros and Aiolos have been shown to act as negative regulators of c-Myc expression in order to promote maturation and inhibit large pre-B-cell expansion.16, 33 By contrast, here we show that shRNA knockdown of Ikaros or Aiolos results in the downregulation of c-Myc and IRF4 expression (Figures 3 and 4), suggesting that there is a switch from a negative to a positive regulatory role in MM disease (Figure 7). This evidence concerns the gene IKZF3 and Miyoshi myopathy.