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Structural and functional Alterations of FLT3 in Acute Myeloid Leukemia

Meshinchi, Soheil and Appelbaum, Frederick R. (2009) Structural and functional Alterations of FLT3 in Acute Myeloid Leukemia. Clinical Cancer Research, 15 (13). pp. 4263-4269. ISSN 1078-0432

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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 leads to autonomous receptor activation, dysregulation of FLT3 signal transduction pathways, contributes 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 would provide a better understanding of the molecular pathogenesis of AML and may provide insights into potential therapeutic interventions.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1158/1078-0432.CCR-08-1123
PubMed ID: 19549778
PMCID: PMC2716016
Grant Numbers: CA114563
Keywords or MeSH Headings: * Gene Duplication * Hematopoiesis/genetics * Humans * Leukemia, Myeloid, Acute/diagnosis * Leukemia, Myeloid, Acute/genetics* * Leukemia, Myeloid, Acute/therapy * Models, Biological * Mutation/physiology* * Prognosis * Protein Structure, Tertiary/genetics * Protein Structure, Tertiary/physiology * Structure-Activity Relationship * fms-Like Tyrosine Kinase 3/chemistry * fms-Like Tyrosine Kinase 3/genetics* * fms-Like Tyrosine Kinase 3/physiology*
Subjects: Cellular and Organismal Processes > Genetic processes > Mutation
Diseases > Hematologic and lymphatic diseases > Leukemia
Therapeutics > Drug Therapy
Depositing User: Library Staff
Date Deposited: 02 Sep 2009 16:22
Last Modified: 14 Feb 2012 14:42

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