IL7R complex as a driver of T-ALL oncogenesis and a therapeutic target. (A) JAK3 mutations cause T-ALL and may or may not require JAK1 depending on whether the mutation affects the pseudokinase or the kinase domain of JAK3, respectively. JAK3 mutations require the cytokine receptor complex for transformation. (B) JAK3 inhibition can reduce the leukemic burden but could not eradicate the leukemia-initiating cells. (C) Cotargeting JAK1 and JAK3 demonstrated synergistic inhibition on the leukemic burden.