The SIGnaling Network
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Pathway ID: SIGNOR-AML-FLT3

Description: FLT3 is a transmembrane class III tyrosine kinase receptor that is activated by the extracellular ligand (FLT3LG)It is expressed by CD34+ hematopoietic stem or progenitor cells and has an important role in the early stages of both the myeloid and the lymphoid lineage development. Mutations of the FMS-like tyrosine kinase 3 (FLT3) gene (chr.13q12) occur in approximately 40% of all AML cases. The internal tandem duplications (ITD) represent approximately 30% of all AML cases and can occur in the juxtamembrane domain (JMD) region or in the FLT3 kinase domain TKD1. The mutated receptor is defective in auto-inhibitory control and constitutively activates the RAS, STAT5 and PI3K/AKT pathways. C/EBP (CCAAT/enhancer-binding protein) and PU.1, transcription factors, both implicated in normal myeloid differentiation, are repressed. FoxO3a-mediated apoptosis is prevented. PMID: 25992210

Curated by: irozzo