Distinct acute lymphoblastic leukemia (ALL)-associated Janus Kinase 3 (JAK3) mutants exhibit different cytokine-receptor requirements and JAK inhibitor specificities

Abstract

Background: JAK3, a tyrosine kinase associated to cytokine receptors, is frequently mutated in leukemia. Results: JAK3L857P induces constitutive signaling independently of cytokine receptors and JAK1, in contrast to other JAK mutants. Conclusion: Different JAK mutants signal through distinct mechanisms and show different sensitivity to JAK1- or JAK3- specific inhibitors. Significance: Depending on the JAK residue mutated, patients will require different treatments.