Signal transducer and activator of transcription (STAT) proteins are latent transcription factors that mediate a wide range of actions induced by cytokines, interferons, and growth factors. We now report the development of thymic T cell lymphoblastic lymphomas in transgenic mice in which Stat5a or Stat5b is overexpressed within the lymphoid compartment. The rate of lymphoma induction was markedly enhanced by immunization or by the introduction of TCR transgenes. Remarkably, the Stat5 transgene potently induced development of CD8+ T cells, even in mice expressing a class II-restricted TCR transgene, with resulting CD8+ T cell lymphomas. These data demonstrate the oncogenic potential of dysregulated expression of a STAT protein that is not constitutively activated, and that TCR stimulation can contribute to this process.
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http://dx.doi.org/10.1084/jem.20021548 | DOI Listing |
Zhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Blood Diseases Institute, Xuzhou Medical University, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University.
Objective: To explore whether Ph acute lymphoblastic leukemia (ALL) cell line SUP-B15 treated with imatinib occurs a tolerant status charactered by cell proliferation suppression but apoptotic resistance, then evaluate whether IGF1-R inhibitor AEW541 can break this tolerance, and further explain its mechanisms.
Methods: SUP-B15 cells were treated with different concentrations of imatinib or AEW541. Cell proliferation was assayed by Deep Blue, and apoptotic cells were determined by Annexin V/7-AAD staining.
Planta Med
January 2025
Laboratório de Farmacologia Molecular, Instituto de Tecnologia em Fármacos; Fiocruz, Rio de Janeiro, RJ, Brasil.
Chronic myeloid leukemia (CML) is a myeloproliferative disease, characterized by the presence of the oncogene BCR-ABL. Imatinib mesylate (IMA) is the first-line treatment for CML, and some treatment resistance has been reported. Natural products are rich sources of bioactive compounds with biological effects, opening a possibility to alter cell susceptibility to drugs such as imatinib.
View Article and Find Full Text PDFCell Rep Med
July 2024
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Center for RNA Biology and Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA. Electronic address:
Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g.
View Article and Find Full Text PDFSci Immunol
May 2024
Department of Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (T17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment.
View Article and Find Full Text PDFOncogene
November 2023
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China.
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