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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by an accumulation of immature T cells. Although patient outcomes have improved, novel targeted therapies are needed to reduce the intensity of chemotherapy and improve the prognosis of high-risk patients. Interleukin-7 (IL-7) modulates the survival and proliferation of normal and malignant T cells. Targeting the IL-7 signaling pathway is thus a potentially effective therapeutic strategy. To achieve such aim, it is essential to first understand how the IL-7 signaling pathway is activated. Although IL-7 production has been observed from multiple stromal tissues, T-ALL autocrine IL-7 secretion has not yet been described. Interestingly, using T-ALL cell lines, primary and patient-derived xenotransplanted (PDX) T-ALL cells, we demonstrate that T-ALL cells produce IL-7 whereas normal T cells do not. Finally, using knock down of IL7 gene in T-ALL cells, we describe to what extent IL-7 autocrine secretion is involved in the T-ALL cells propagation in bone marrow and how it affects the number of leukemia-initiating cells in PDX mice. Together, these results demonstrate how the autocrine production of the IL-7 cytokine mediated by T-ALL cells can be involved in the oncogenic development of T-ALL and offer novel insights into T-ALL spreading.

Citation

Anne Buffière, Benjamin Uzan, Romain Aucagne, François Hermetet, Manon Mas, Sandra Nassurdine, Aziza Aznague, Virginie Carmignac, Benjamin Tournier, Olivier Bouchot, Paola Ballerini, João T Barata, Jean-Noël Bastie, Laurent Delva, Françoise Pflumio, Ronan Quéré. T-cell acute lymphoblastic leukemia displays autocrine production of Interleukin-7. Oncogene. 2019 Nov;38(48):7357-7365

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PMID: 31417180

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