IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia
| Autor: | João T. Barata, Daniel Dias Ribeiro, Alice Melão |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
medicine.medical_treatment T cell Antineoplastic Agents Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 03 medical and health sciences Mice 0302 clinical medicine Genetics medicine Animals Humans Receptor Interleukin-7 receptor Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway STAT5 030304 developmental biology 0303 health sciences Clinical Trials as Topic Receptors Interleukin-7 Interleukin-7 Immunotherapy 3. Good health Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology biology.protein Molecular Medicine Signal Transduction |
| Zdroj: | Advances in Biological Regulation |
| ISSN: | 2212-4934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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