Originally published as JCO Early Release 10.1200/JCO.2008.21.3264 on August 10 2009

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Targeting Signal Transducer and Activator of Transcription Signaling Pathway in Leukemias

From the Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey; Department of Molecular and Cellular Biology and Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.

Corresponding author: Meir Wetzler, MD, Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263; e-mail: Meir.Wetzler{at}Roswellpark.org.

Signal transducer and activator of transcription (STAT) proteins comprise a seven-member family of latent cytoplasmic transcription factors that are activated through tyrosine phosphorylation by a variety of cytokines and growth factors. Aberrant activation of STATs accompanies malignant cellular transformation with resultant leukemogenesis. Constitutive activation of STATs has been demonstrated in various leukemias. A better understanding of the mechanisms of dysregulation of the STAT pathway and understanding of the cause and effect relationship in leukemogenesis may serve as a basis for designing novel therapeutic strategies directed against STATs. Mechanisms of STAT activation, the potential role of STAT signaling in leukemogenesis, and recent advances in drug discovery targeting the STAT pathway are the focus of this review.

Supported in part by Grants No. CA16056, CA85580, and CA99238 from the National Cancer Institute, Bethesda, MD, and The Heidi Leukemia Research Fund, Buffalo, NY.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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