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Signal transducer and activator of transcription (STAT)-5: an opportunity for drug development in oncohematology

Oncogene volume 38, pages 4657–4668 (2019)Cite this article

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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.

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Acknowledgements

We thank all the authors that contributed to the understanding of the role of STAT5 in hematopoiesis and oncohematology. We apologize to those whose work deserves to be cited but unfortunately are not quoted because of space restriction. The research program in the author’s lab was supported by grants-in-aid from Spanish Ministry of Economy and Competitivity (MINECO) with the funding of European Regional Development Fund-European Social Fund (SAF2015-65113-C2-2-R) and Alfredo Martin-Reyes Foundation (Arehucas) - FICIC. CR and MMG were supported by postdoctoral grants-in-aid from MINECO - Juan de la Cierva 2017 program and ULPGC 2017, respectively.

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  1. Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Universidad de Las Palmas de Gran Canaria, Farmacología Molecular y Traslacional - BIOPharm, Las Palmas de G.C., 35016, Las Palmas, Spain

    Carlota Recio, Borja Guerra, Miguel Guerra-Rodríguez, Haidée Aranda-Tavío, Patricia Martín-Rodríguez, Mercedes de Mirecki-Garrido, Yeray Brito-Casillas, José M. García-Castellano & Leandro Fernández-Pérez

  2. Instituto Universitario de Bio-Orgánica (CIBICAN), Departamento de Química Orgánica, Universidad de La Laguna, 38206, Tenerife, Spain

    Ana Estévez-Braun

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Recio, C., Guerra, B., Guerra-Rodríguez, M. et al. Signal transducer and activator of transcription (STAT)-5: an opportunity for drug development in oncohematology. Oncogene 38, 4657–4668 (2019). https://doi.org/10.1038/s41388-019-0752-3

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