The Emerging Role of Suppressors of Cytokine Signaling (SOCS) in the Development and Progression of Leukemia
1
Department of Pediatrics, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
2
Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM 87131, USA
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(16), 4000; https://doi.org/10.3390/cancers13164000
Submission received: 2 July 2021
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Revised: 4 August 2021
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Accepted: 6 August 2021
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Published: 8 August 2021
Simple Summary
The suppressors of cytokine signaling (SOCS) are known cytokine-inducible negative regulators of JAK/STAT and other cell signaling pathways. Deregulation of SOCS expression is linked to various tumor types and inflammatory diseases. While SOCS play a crucial role in the regulation of immune cell function, their roles in hematological malignancies have not been elucidated thus far. In this review, we summarize the current knowledge on the roles of SOCS in leukemia development and progression. We delineate the paradoxical activities of SOCS in different leukemia types and the regulatory mechanisms underlying SOCS deregulation in leukemia. Lastly, we discuss the possible implications of SOCS deregulation for leukemia diagnosis and prognosis. This paper provides new insights into the roles of SOCS in the pathobiology of leukemia and leukemia research.
Abstract
Cytokines are pleiotropic signaling molecules that execute an essential role in cell-to-cell communication through binding to cell surface receptors. Receptor binding activates intracellular signaling cascades in the target cell that bring about a wide range of cellular responses, including induction of cell proliferation, migration, differentiation, and apoptosis. The Janus kinase and transducers and activators of transcription (JAK/STAT) signaling pathways are activated upon cytokines and growth factors binding with their corresponding receptors. The SOCS family of proteins has emerged as a key regulator of cytokine signaling, and SOCS insufficiency leads to constitutive activation of JAK/STAT signaling and oncogenic transformation. Dysregulation of SOCS expression is linked to various solid tumors with invasive properties. However, the roles of SOCS in hematological malignancies, such as leukemia, are less clear. In this review, we discuss the recent advances pertaining to SOCS dysregulation in leukemia development and progression. We also highlight the roles of specific SOCS in immune cells within the tumor microenvironment and their possible involvement in anti-tumor immunity. Finally, we discuss the epigenetic, genetic, and post-transcriptional modifications of SOCS genes during tumorigenesis, with an emphasis on leukemia.
