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Oncogene ; 38(48): 7357-7365, 2019 11.
Article in English | MEDLINE | ID: mdl-31417180

ABSTRACT

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.


Subject(s)
Autocrine Communication , Bone Marrow/immunology , Interleukin-7/biosynthesis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , T-Lymphocytes/immunology , Animals , Apoptosis , Bone Marrow/metabolism , Bone Marrow/pathology , Cell Proliferation , Female , Humans , Male , Mice , Mice, Inbred NOD , Mice, SCID , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
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