title: IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia.
abstract: Interleukin-7 (IL-7), a cytokine produced in the bone marrow, thymus and other organs, is mandatory for normal human T-cell development and peripheral homeostasis. Different studies, including phase I clinical trials, have indicated the potential therapeutic value of recombinant IL-7 in the context of anti-cancer immunotherapy and as a booster of immune reconstitution. However, the two main pathways activated by IL-7, JAK/STAT5 and PI3K/Akt/mTOR, have both been implicated in cancer and there is considerable evidence that IL-7 and its receptor (IL-7R), formed by IL-7Rα (encoded by IL7R) and γc, may partake in T-cell acute lymphoblastic leukemia (T-ALL) development. In this context, the most compelling data comes from recent studies demonstrating that around 10% of T-ALL patients display IL7R gain-of-function mutations leading, in most cases, to disulfide bond-dependent homodimerization of two mutant receptors and consequent constitutive activation of downstream signaling, with ensuing cell transformation in vitro and tumorigenic ability in vivo. Here, we review the data on the involvement of IL-7 and IL-7R in T-ALL, further discussing the peculiarities of IL-7R-mediated signaling in human leukemia T-cells that may be of therapeutic value, namely regarding the potential use of PI3K and mTOR pharmacological inhibitors.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Unversidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ribeiro
authors.forename: Alice
authors.initials: A
authors.lastname: Melão
authors.forename: João T
authors.initials: JT
authors.lastname: Barata
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000503:physiopathology; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain