Deregulation of the JAK-STAT signaling cascade in T-ALL. Representation of the different oncogenic mechanisms that lead to aberrant activation of the IL7 signaling in T-ALL. Interaction of IL7 with the heterodimeric IL7R induces reciprocal JAK1 and JAK3 phosphorylation and subsequent recruitment of STAT5. STAT5 dimerizes and translocates to the nucleus where it induces transcription of the prosurvival factor BCL2. IL7 also activates the RAS-MAPK and PI3K kinase pathways. IL7 signaling can indirectly be enhanced by abnormal NOTCH1 signaling, constitutive expression of ZEB2, or by increased presentation of IL7R on the cell surface of thymocytes due to impaired clathrin-dependent endocytosis caused by DNM2 mutations. Promising therapeutic agents targeting the oncogenic IL7-JAK-STAT cascade are indicated in red. *Proteins that are mutated in T-ALL.