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STAT signaling in the pathogenesis and treatment of leukemias

Oncogene volume 19, pages 2496–2504 (2000)Cite this article

Abstract

Leukemias continue to cause significant mortality in adults and children, and the use of standard cytotoxic chemotherapy has reached a therapeutic plateau. Thus, there is great interest in treatments directed against inappropriately activated cell signaling pathways which stimulate the uncontrolled growth of neoplastic cells. Increasing evidence suggests that the STAT signaling cascade may be one target of these therapies. Signal transducer and activator of transcription (STAT) proteins are critical in mediating the response of hematopoietic cells to a diverse spectrum of cytokines. Constitutive STAT activation is present in many malignancies and has been especially well characterized in acute and chronic leukemias. While STAT activation is a common characteristic of leukemias, the specific pattern of activated STATs and the manner by which STAT activation occurs vary with each disease. STAT tyrosine phosphorylation can occur through inappropriate Jak activation or by direct activation of an oncoprotein such as Bcr/Abl, and STAT serine phosphorylation may play an important role in leukemias as well. Thus, the STAT signaling pathway is an attractive target for therapeutic intervention, and strategies designed to inhibit STAT activation and STAT mediated gene transcription may play an important role in the next generation of anti-leukemia therapies.

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Acknowledgements

This work was supported by NIH grant CA79547 and the Brent Leahey Fund.

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Author notes

  1. Thomas S Lin and Sudipta Mahajan: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Adult Oncology, Dana Farber Cancer Institute, Boston, 02115, Massachusetts, MA, USA

    Thomas S Lin, Sudipta Mahajan & David A Frank

  2. Department of Medicine, Brigham and Woman's Hospital, Boston, 02115, Massachusetts, MA, USA

    Thomas S Lin, Sudipta Mahajan & David A Frank

  3. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Thomas S Lin, Sudipta Mahajan & David A Frank

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Lin, T., Mahajan, S. & Frank, D. STAT signaling in the pathogenesis and treatment of leukemias. Oncogene 19, 2496–2504 (2000). https://doi.org/10.1038/sj.onc.1203486

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