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The Role of Signal Transducer and Activator of Transcription Factors in Leukemogenesis

From the Brigham and Women's Hospital, Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA

Address reprint requests to David W. Sternberg, MD, PhD, Hematology Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115; e-mail: dsternberg{at}partners.org

Human leukemias are frequently associated with the aberrant expression of activated fusion tyrosine kinases or activated protein tyrosine kinases carrying insertional or point mutations. The activated kinase enzymes typically phosphorylate one or more signal transducer and activator of transcription (STAT) factors, which translocate to the cell nucleus and regulate the expression of genes associated with survival and proliferation. The phosphorylation and activation of STAT family members has been described in a wide range of human leukemias. Furthermore, animal models of leukemia have demonstrated the pivotal contribution of STAT activation to leukemic pathogenesis. This review discusses evidence for the functional importance of STAT activation in the biology of leukemia and current opportunities for modulating STAT proteins in the therapy of this group of diseases.

Supported by National Institutes of Health grant CA82261 (D.W.S.), and National Institutes of Health grants CA66996 and DK50654; a grant from the Leukemia and Lymphoma Society; and the Howard Hughes Medical Institute (D.G.G.).

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

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