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Title: Signal transducer and activator of transcription (STAT)-5: an opportunity for drug development in oncohematology
Authors: Recio Cruz, Carlota Pilar 
Guerra, Borja 
Guerra Rodríguez, Miguel Alfonso 
Aranda Tavío, Haidee Magdalena 
Martín-Rodríguez, Patricia 
de Mirecki-Garrido, Mercedes 
Brito-Casillas, Yeray 
García-Castellano, José M.
Estévez-Braun, Ana
Fernández Pérez, Leandro Fco 
UNESCO Clasification: 320101 Oncología
3207 Patología
Keywords: Chronic Myeloid-Leukemia
Hodgkin Lymphoma
Janus Kinases
Stat Proteins
Self-Renewal, et al
Issue Date: 2019
Project: Desarrollo Preclínico de Nuevas Estructuras Bioactivas Moduladoras de Las Actividades Oncogénicas de Stat3/5 O de Los Receptores de Estrógenos 
Journal: Oncogene 
Abstract: The signal transducer and activator of transcription (STAT) are transcription factors that work via JAK/STAT pathway regulating the expression of genes involved in cell survival, proliferation, differentiation, development, immune response, and, among other essential biological functions, hematopoiesis. JAK/STAT signaling is strictly regulated under normal physiological conditions. However, a large group of diverse diseases has been associated to an aberrant regulation of STAT factors. Erroneous modulation of the pathway leads to constitutive STAT activation, thereby driving proliferation, inflammation, and an uncontrolled immune response. Deregulated STAT5 activation has been found in the development of many hematopoietic tumors, including chronic and acute leukemias, polycythemia vera, and lymphoma. Mutations in the kinases that phosphorylate STAT5, and/or overexpression of the upstream receptor-associated tyrosine kinases have been suggested as the main drivers of constitutive STAT5 activation. Hyper-activated STAT5 leads to the aberrant expression of its target genes including antiapoptotic, proliferative, and pro-inflammatory genes, favouring tumorigenesis. In this review, we intent to discuss the biology of JAK/STAT pathway, with particular focus on STAT5 and its crucial role in the development and progression of hematologic malignancies. Furthermore, we provide a synopsis of potential therapeutic strategies based on STAT5 activity inhibition that may represent an excellent opportunity for drug development in oncohematology.
ISSN: 0950-9232
DOI: 10.1038/s41388-019-0752-3
Source: Oncogene [ISSN 0950-9232], v. 38 (24), p. 4657-4668
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