Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Oncogenic Signaling in Acute Myeloid Leukemia

Author(s): Christian H. Brandts, Wolfgang E. Berdel, Hubert Serve.

Abstract:

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow. Despite intensive treatment only one third of AML patients are cured. Numerous genetic events have been identified in the last years that have shed light into the mechanisms dictating increased self-renewal, proliferation, survival and block in differentiation. It is increasingly recognized that AML represents a hierarchical disease, originating from a leukemia stem cell population. Sophisticated animal models have helped to elucidate rate-limiting steps in initiation, development and maintenance of AML. This review discusses the fundamental genetic events identified to date that determine the pathogenesis of AML, with particular emphasis on the oncogenic signaling events that result from translocation of myeloid transcription factors and mutations in receptor tyrosine kinases. Our current understanding of the biology of AML has fueled the development of promising anti-leukemic agents, which may improve the treatment of the disease in the future.

Keywords: Acute promyelocytic leukemia (APL), core binding factor (CBF), GATA-1 mutation, Nucleophosmin (NPM), MLL protein, Hox homeodomain proteins

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Article Details

VOLUME: 8
ISSUE: 2
Year: 2007
Page: [237 - 246]
Pages: 10
DOI: 10.2174/138945007779940197
Price: $58