Moreover, gain-of-function alterations in the IL-7 pathway also result in the activation of PI3K-AKT and Ras-MAPK signaling, and although treatment with small molecule inhibitors targeting PI3K, AKT or MEK alone were not effective, inhibiting both the PI3K-AKT and Ras-MAPK pathway synergistically reduced the cytokine-independent proliferation of Ba/F3 cells expressing mutant IL-7Rα, JAK1 or JAK3, as well as primary T-ALL cells [24]. Here, JAK3 is linked to acute lymphoblastic leukemia.