STAT3 and neoplasm: Cytokine signaling is also corrupted in clinically aggressive CLL cells that harbor mutations of ATM or TP53. Type 1 IFN inhibits growth of indolent CLL cells and activates the canonical signaling pathway, characterized by prolonged phosphorylation of STAT1 and brief phosphorylation of STAT3. In aggressive CLL cells, IFN causes prolonged STAT3 phosphorylation associated with immunosuppressive factor production and tumor growth in vitro (53).