We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic c...

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 spec...

In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML. The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting through its ubiquitin ligase activity and as a platform for several signaling adap...

*BS and CC contributed equally to the work presented hereAbstract In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML. The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting through its ubiq...

Activating fetal liver tyrosine kinase 3 (Flt3) mutations represent the most common genetic aberrations in acute myeloid leukemia (AML). Most commonly, they occur as internal tandem duplications in the juxtamembrane domain (Flt3-ITD) that transform myeloid cells in vitro and in vivo and that induce aberrant signaling and biologic functions. We identified RGS2, a regulator of G-protein signaling...

background & objectives: anaplastic lymphoma kinase (alk) is a receptor tyrosine kinase involved in the genesis of several human cancers. alk was initially identified because of its involvement in anaplastic large cell lymphoma (alcl). alk is believed to foster tumorigenesis following activation by autocrine and/or paracrine growth loops. studies reveal that the presence of anti-alk antibod...

The inhibition of FMS-like tyrosine kinase 3 (FLT3) activity using small-molecule inhibitors has emerged as a target-based alternative to traditional chemotherapy for the treatment of acute myeloid leukemia (AML). In this study, we report the use of structure-based virtual screening (SBVS), a computer-aided drug design technique for the identification of new chemotypes for FLT3 inhibition. For ...

Fetal liver tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutations are the most common molecular abnormality associated with adult acute myeloid leukemia (AML). To exploit this molecular target, a number of potent and specific FLT3 kinase inhibitors have been developed and are currently being tested in early phase clinical trials of patients with refractory AML. To explore the effic...

Internal tandem duplication mutations in the Flt3 tyrosine kinase gene (ITD-Flt3) and overexpression of Survivin are frequently found in patients with acute myeloid leukemia (AML). We investigated whether Survivin mediates the enhanced survival of primary hematopoietic progenitor cells (HPCs) resulting from ITD-Flt3 signaling. Ectopic ITD-Flt3 mutants increased Survivin expression in Ba/F3 cell...

Activating fetal liver tyrosine kinase 3 (Flt3) mutations represent the most common genetic aberrations in acute myeloid leukemia (AML). Most commonly, they occur as internal tandem duplications in the juxtamembrane domain (Flt3-ITD) that transform myeloid cells in vitro and in vivo and that induce aberrant signaling and biologic functions. We identified RGS2, a regulator of G-protein signaling...