Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor

A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations.

Internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3 have been found in 20% to 30% of patients with acute myeloid leukemia (AML). These mutations constitutively activate the receptor and appear to be associated with a poor prognosis. Recent evidence that this constitutive activation is leukemogenic renders this receptor a potential target for specific therapy. In thi...

FMS-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD): a villain among others

cute myeloid leukemia (AML) is the most frequent acute eukemia of adult patients with an estimated 10,070 new cases n Brazil in 2016. Most of the cases are de novo, without a efined etiology, and around two thirds of the patients will die f the disease, according to the Instituto Nacional de Câncer INCA).1 Genetic aberrations may help to differentiate patients ho have a good from those with a d...

Sorafenib in Relapsed AML With FMS-Like Receptor Tyrosine Kinase-3 Internal Tandem Duplication Mutation.

Old age (≤65 years), relapsed or refractory disease, and the presence of FMS-like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation are poor prognostic factors in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib have been shown to have a potential role in treating relapsed or refractory AML with FLT3 mutations. In the present report, the use of sorafeni...

Cooperation between the partial tandem duplication of Mll (Mll PTD) and internal tandem duplication of FLT3 (FLT3 ITD) in the pathogenesis of acute myeloid leukemia (AML)

An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients.

PURPOSE Obtaining direct and rapid proof of molecular activity in early clinical trials is critical for optimal clinical development of novel targeted therapies. SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms-related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor tyr...