Figure 1. Constitutively activated growth factor receptors deregulate polycomb complexes via MAPKAP3 kinase, leading to the deregulation of PAX5 gene in t(8;21) AML. Left panel: Receptor tyrosine kinases on binding to their respective ligands signal to the nucleus of the cell via JAK/STAT, MEK/JNK, and p38 pathways in a regulated manner. Right panel: In t(8;21) AML activating mutations constitutively activates receptor tyrosine kinases that, in turn, constitutively activates downstream kinases JAK/STAT, MEK/JNK, and p38. STAT3 provides survival a signal to t(8;21) cells. JNK, MEK, and p38 constitutively activate MAPKAPK3 (3pK), which leads to the dissociation of polycomb from PAX5 leading its aberrant activation.