Mutant FLT3 signaling contributes to a block in myeloid differentiation

Rui Zheng, Donald Small

Research output: Contribution to journalArticle

Abstract

FLT3 is a member of the class III receptor tyrosine kinase family and is primarily expressed on hematopoietic stem/progenitor cells. Somatic mutations of FLT3 involving internal tandem duplication (ITD) of the juxtamembrane domain or point mutations in the activation loop have been identified in ∼ 17 - 34% and 7 - 9% of acute myeloid leukemia (AML) patients, respectively. The ITD mutations appear to activate the tyrosine kinase domain through receptor dimerization in a FLT3 ligand-independent manner. Constitutively activated FLT3 provides cells with proliferative and anti-apoptotic advantages and portends an especially poor prognosis for patients with this mutation. FLT3/ITD mutations also contribute to a block of myeloid differentiation. FLT3 tyrosine kinase inhibitors suppress the growth and induce apoptosis and differentiation of leukemia cells expressing FLT3/ITD mutants. Therefore, FLT3 is a therapeutic target and inhibition of FLT3 tyrosine kinase activity may provide a new approach in the treatment of leukemia carrying these mutations.

Original languageEnglish (US)
Pages (from-to)1679-1687
Number of pages9
JournalLeukemia and Lymphoma
Volume46
Issue number12
DOIs
StatePublished - Dec 1 2005

Keywords

  • Mutant FLT3
  • Myeloid differentiation
  • Signaling

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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