Janus Kinase Signaling: Oncogenic Criminal of Lymphoid Cancers

SIMPLE SUMMARY: Janus kinases (JAKs) are transmembrane receptors that pass signals from extracellular ligands to downstream. Increasing evidence has suggested that JAK family aberrations promote lymphoid cancer pathogenesis and progression through mediating gene expression via the JAK/STAT pathway or noncanonical JAK signaling. We are here to review how canonical JAK/STAT and noncanonical JAK signalings are represented and deregulated in lymphoid malignancies and how to target JAK for therapeutic purposes. ABSTRACT: The Janus kinase (JAK) family are known to respond to extracellular cytokine stimuli and to phosphorylate and activate signal transducers and activators of transcription (STAT), thereby modulating gene expression profiles. Recent studies have highlighted JAK abnormality in inducing over-activation of the JAK/STAT pathway, and that the cytoplasmic JAK tyrosine kinases may also have a nuclear role. A couple of anti-JAK therapeutics have been developed, which effectively harness lymphoid cancer cells. Here we discuss mutations and fusions leading to JAK deregulations, how upstream nodes drive JAK expression, how classical JAK/STAT pathways are represented in lymphoid malignancies and the noncanonical and nuclear role of JAKs. We also summarize JAK inhibition therapeutics applied alone or synergized with other drugs in treating lymphoid malignancies.