Figure 8.

Schematic model of acute lymphoblastic leukemia induction by mutant human IL7R and NRAS. (A) mutIL7R induced expression of BCL2 by JAK/STAT signal. p-JAK-1 phosphorylates STAT-5, which activated its transcription activity. This leads to increased levels of BCL2 mRNA and protein. MutNRAS contributes to MYC stabilization through Raf/ERK and PI3K/AKT activation. The Raf/ERK pathway increases the stable form of MYC by phosphorylation of (Ser62). In addition, the PI3K/AKT signal contributes indirectly to MYC stability by increasing p-AKT and inhibiting GSK-3 activity, which results in inhibition of MYC degradation. (B) PLK-1 that is positively regulated by MYC activity can contribute to MYC stabilization through inhibition of FBXW-7, which leads to inhibition of MYC proteasomal degradation and creates a positive feedback loop.