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URL http://www.rockymountainbmt.com/news/Extracellular-KIT-receptor-mutants-found-in-acute-myelogenous-leukemia-AML-respond-to-imatinib-mesylate-2673.html

Extracellular KIT receptor mutants, found in acute myelogenous leukemia (AML), respond to imatinib mesylate

08-18-2006

According to a study from Germany, "Multiple genetic alterations are required to induce AML. Mutations in the extracellular domain of the KIT receptor are almost exclusively found in patients with AML carrying translocations or inversions affecting members of the core binding factor (CBF) gene family and correlate with a high risk of relapse."

"We demonstrate that these complex insertion and deletion mutations lead to constitutive activation of the KIT receptor, which induces factor-independent growth of interleukin-3 (IL-3) dependent cells. Mutation of the evolutionary conserved amino acid D419 within the extracellular domain was sufficient to constitutively activate the KIT receptor, although high expression levels were required. Dose-dependent growth inhibition and apoptosis were observed using either the protein tyrosine kinase inhibitor imatinib mesylate (ST1571, Gleevec) or by blocking the phosphoinositide-3-kinase (PI3K)-AKT pathway," explained J. Cammenga and colleagues, Universitatsklinikum Hamburg-Eppendorf.

The researchers concluded, "Our data show that the addition of kinase inhibitors to conventional chemotherapy might be a new therapeutic option for CBF-AML expressing mutant KIT."

Cammenga and colleagues published the results of their research in Blood (Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate. Blood, 2005;106(12):3958-3961).

For additional information, contact C. Stocking, Universitatsklinikum Hamburg-Eppendorf, Pathology Group, Heinrich Pette Institute Experimental Virology & Immunology, POB 201 652, D-20206 Hamburg, Germany.

Keywords: Hamburg, Germany, Apoptosis, Biotechnology, Chemotherapy, Drug Development, Cancer Drugs, Genetics, Hematology, Imatinib Mesylate, Leukemia, Pharmaceuticals, Proteins, Proteomics, Cancer Therapy, Tyrosine Kinase, Kinase Inhibitor.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.