Deregulation of the Interleukin-7 Signaling Pathway in Lymphoid Malignancies

The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphoid cell development. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function alterations in the pathway contribute to malignant transformation of lymphocytes. Binding of IL-7 to the IL-7 receptor results in the activation of the JAK-STAT, PI3K-AKT and Ras-MAPK pathways, each contributing to survival, cell cycle progression, proliferation and differentiation. Here, we discuss the role of deregulated IL-7 signaling in lymphoid malignancies of B- and T-cell origin. Especially in T-cell leukemia, more specifically in T-cell acute lymphoblastic leukemia and T-cell prolymphocytic leukemia, a high frequency of mutations in components of the IL-7 signaling pathway are found, including alterations in IL7R, IL2RG, JAK1, JAK3, STAT5B, PTPN2, PTPRC and DNM2 genes.