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PMID: 19549778 Published · ppublish English Journal Article Review

Structural and functional alterations of FLT3 in acute myeloid leukemia.

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 15 ·No. 13 ·2009-07-01 ·Pages 4263-9

Meshinchi S, Appelbaum FR

Abstract

Hematopoiesis is highly regulated through cytokine-induced stimulation of multiple signal transduction pathways in order to mediate appropriate differentiation and proliferation of specific progenitor populations. Ligand-induced stimulation of the FMS-like tyrosine kinase 3 (FLT3) leads to activation of multiple downstream effector pathways resulting in differentiation and proliferation of specific progenitor cell populations. Genomic alterations of the FLT3 gene, including FLT3 internal tandem duplication (FLT3/ITD) and FLT3 activation loop mutation (FLT3/ALM) lead to autonomous receptor activation, dysregulation of FLT3 signal transduction pathways, contribute to myeloid pathogenesis, and have been linked to response to therapy and clinical outcome. Exploring the mechanisms by which these FLT3 alterations lead to dysregulated proliferation should provide a better understanding of the molecular pathogenesis of acute myeloid leukemia (AML) and may provide insights into potential therapeutic interventions. FLT3 inhibitors are under evaluation for their efficacy in AML patients with FLT3 mutations.

MeSH Terms
Gene Duplication Hematopoiesis/genetics Humans Leukemia, Myeloid, Acute/diagnosis,genetics,therapy Models, Biological Mutation/physiology Prognosis Protein Structure, Tertiary/genetics,physiology Structure-Activity Relationship fms-Like Tyrosine Kinase 3/chemistry,genetics,physiology
Chemicals
FLT3 protein, human fms-Like Tyrosine Kinase 3
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Meshinchi Soheil
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. smeshinc@fhcrc.org
Appelbaum Frederick R
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Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-08-1123
Email
smeshinc@fhcrc.org
Published
2009-07-01
Epub
2009-00-23
Pages
4263-9
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC2716016
Subset
IM
Grants
NCI NIH HHS · R01 CA114563 · United States
NCI NIH HHS · R01 CA114563-04 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-08-1123 PMC Full Text View journal details
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