%0 Journal Article %1 Spiekermann.2003 %A Spiekermann, K. %A Bagrintseva, K. %A Schwab, R. %A Schmieja, K. %A Hiddemann, W. %D 2003 %J Clin.Cancer Res. %K 3 Acid Activation Acute Amino Cell DNA-Binding Data Enzyme Factor Human Humans Indoles Kinase Kinases Leukemia Milk Mitogen-Activated Molecular Mutation Myeloid Neoplastic Phenotype Phosphorylation Protein Protein-Tyrosine Proteins Proto-Oncogene Receptor Research STAT3 STAT5 Sequence Trans-Activators Transcription Transformation Tyrosine cells fms-Like metabolism pathology pharmacology physiology protein response therapy %N 6 %P 2140-2150 %T Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells %U PM:12796379 %V 9 %X PURPOSE: Activating length mutations in the juxtamembrane domain (FLT3-LM) and mutations in the tyrosine kinase domain (FLT3-TKD) of FLT3 represent the most frequent genetic alterations in acute myeloid leukemia (AML). However, the functional role of active FLT3 mutants in primary AML blast cells is not well characterized. EXPERIMENTAL DESIGN: We analyzed the transforming potential and the signaling of FLT3-ITD mutants in Ba/F3 cells and in primary AML blasts. RESULTS: FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation. In contrast to the FLT3-ITD mutants, the ligand-stimulated FLT3-WT receptor was unable to transduce a fully proliferative response in Ba/F3 and monocytic OCI-AML5 cells. The ligand-stimulated FLT3-WT receptor activated AKT and MAPK, but not STAT5. In primary blast cells from 60 patients with AML, FLT3 was expressed in 91.9% of patients

@article{Spiekermann.2003, abstract = {PURPOSE: Activating length mutations in the juxtamembrane domain (FLT3-LM) and mutations in the tyrosine kinase domain (FLT3-TKD) of FLT3 represent the most frequent genetic alterations in acute myeloid leukemia (AML). However, the functional role of active FLT3 mutants in primary AML blast cells is not well characterized. EXPERIMENTAL DESIGN: We analyzed the transforming potential and the signaling of FLT3-ITD mutants in Ba/F3 cells and in primary AML blasts. RESULTS: FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation. In contrast to the FLT3-ITD mutants, the ligand-stimulated FLT3-WT receptor was unable to transduce a fully proliferative response in Ba/F3 and monocytic OCI-AML5 cells. The ligand-stimulated FLT3-WT receptor activated AKT and MAPK, but not STAT5. In primary blast cells from 60 patients with AML, FLT3 was expressed in 91.9% of patients }, added-at = {2010-02-05T11:28:39.000+0100}, author = {Spiekermann, K. and Bagrintseva, K. and Schwab, R. and Schmieja, K. and Hiddemann, W.}, biburl = {https://www.bibsonomy.org/bibtex/2dcd4cc2ed8e0bb113931393fabbf2889/kanefendt}, interhash = {dd5f2fe31913a83f265ad198de7a3b08}, intrahash = {dcd4cc2ed8e0bb113931393fabbf2889}, journal = {Clin.Cancer Res.}, keywords = {3 Acid Activation Acute Amino Cell DNA-Binding Data Enzyme Factor Human Humans Indoles Kinase Kinases Leukemia Milk Mitogen-Activated Molecular Mutation Myeloid Neoplastic Phenotype Phosphorylation Protein Protein-Tyrosine Proteins Proto-Oncogene Receptor Research STAT3 STAT5 Sequence Trans-Activators Transcription Transformation Tyrosine cells fms-Like metabolism pathology pharmacology physiology protein response therapy}, number = 6, pages = {2140-2150}, timestamp = {2010-02-05T11:28:39.000+0100}, title = {Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells}, url = {PM:12796379}, volume = 9, year = 2003 }