T-cell acute lymphoblastic leukemia displays autocrine production of Interleukin-7

• Published in: Oncogene 2019-11, Vol.38 (48), p.7357-7365
• Main Authors: Buffière, Anne, Uzan, Benjamin, Aucagne, Romain, Hermetet, François, Mas, Manon, Nassurdine, Sandra, Aznague, Aziza, Carmignac, Virginie, Tournier, Benjamin, Bouchot, Olivier, Ballerini, Paola, Barata, João T., Bastie, Jean-Noël, Delva, Laurent, Pflumio, Françoise, Quéré, Ronan
• Format: Article
• Language: English
• Subjects: 13/109; 13/31; 14/1; 631/67/1990/283/2125; 631/80/304; 82/80; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Animals; Apoptosis; Autocrine Communication; Autocrine signalling; Bone marrow; Bone Marrow - immunology; Bone Marrow - metabolism; Bone Marrow - pathology; Brief Communication; Cancer; Cell Biology; Cell Proliferation; Chemotherapy; Cytokines; Female; Genes; Health aspects; Human Genetics; Humans; Interleukin 7; Interleukin-7 - biosynthesis; Interleukins; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Male; Malignancy; Medical prognosis; Medicine; Medicine & Public Health; Mice; Mice, Inbred NOD; Mice, SCID; Oncology; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Risk groups; Signal transduction; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-019-0921-4

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.