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 Blood, 1 January 2005, Vol. 105, No. 1, pp. 22-30.
Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2003-11-3896.

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REVIEW IN TRANSLATIONAL HEMATOLOGY

After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies

Martha Wadleigh, Daniel J. DeAngelo, James D. Griffin, and Richard M. Stone

From the Leukemia Program, Division of Hematologic Malignancy, Department of Medical Oncology, Dana Farber Cancer Institute; and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Tyrosine kinases phosphorylate proteins on tyrosine residues, producing a biologic signal that influences many aspects of cellular function including cell growth, proliferation, differentiation, and death. Constitutive or unregulated activity through mutation or overexpression of these enzymes is a common pathologic feature in many acute and chronic leukemias. Inhibition of tyrosine kinases represents a strategy to disrupt signaling pathways that promote neoplastic growth and survival in hematologic malignancies and likely in other neoplasias as well. This review focuses on tyrosine kinases that have been implicated in the pathogenesis of hematologic diseases other than chronic myelogenous leukemia and discusses the evidence for the use of small molecules to target these kinases.


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