Author: Advani, A. S.

Source: Current Pharmaceutical Design, Volume 11, Number 26, October 2005 , pp. 3449-3457(9)

Publisher: Bentham Science Publishers

Abstract:

Acute myelogenous leukemia (AML) is a difficult disease to treat, and better treatments are needed. Molecular targeted therapy represents a novel therapeutic approach. The FLT3 tyrosine kinase receptor is mutated in approximately one-fourth to one-third of patients with AML. Normally, binding of FLT3 ligand to the FLT3 receptor leads to phosphorylation of tyrosine residues and activation of the receptor. This in turn leads to induction of intracellular signaling pathways essential to regulation of cell proliferation and apoptosis. Two classes of FLT3 activating mutations have been identified in AML patients: internal tandem duplications (ITDS) and point mutations in the activating loop of the kinase domain. Both mutations result in constitutive FLT3 tyrosine kinase activity and lead to transformation of hematopoietic cell lines in vivo and in vitro. FLT3 ITDs are also an independent poor prognostic factor for overall survival and disease free survival in patients with AML. Therefore, targeting FLT3 mutations represents a potential therapeutic target for AML.

This review will discuss the biology and clinical significance of FLT3 and FLT3 mutations in cell growth and signaling. In addition, I will discuss some of the novel FLT3 inhibitors which are entering clinical trials for AML.

Keywords: acute myelogenous leukemia; flt mutations; targeted therapy; flt inhibitors

Document Type: Review article

DOI: http://dx.doi.org/10.2174/138161205774370807

Affiliations: 1: The Cleveland Clinic Lerner College of Medicine, Department of Hematology/ Medical Oncology, The Cleveland Clinic Foundation, Desk R35, 9500 Euclid Avenue, Cleveland, OH 44195.

Publication date: 2005-10-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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