NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases

Figure 1

The STAT3 signalling pathway in ALK+ ALCL. STAT3 is activated by NPM-ALK signalling, but reports differ as to whether this is JAK3-dependent or independent. The phosphatase, PP2A, and signalling through the IL-9, IL-21, and IL-22 receptors also promote STAT3 activation in ALK+ ALCL. STAT3 promotes the expression of genes that suppress apoptosis and enhance proliferation in ALK+ ALCL. STAT3 can also repress a variety of genes in this malignancy through DNA methylation. Suppression of the SHP1 phosphatase by STAT3 is particularly important in ALK+ ALCL, as SHP1 inhibits NPM-ALK and STAT3 activity.