Tumors with activated EGF receptors can be treated with drugs that inhibit the kinase activity by binding to intracellular domains. Most of these drugs are ATP analogs that block ATP binding and thus prevent auto- and transphosphorylation by the intracellular receptor domains. Mutations...
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The gene product of the BCR-ABL1 fusion gene is a kinase with a higher activity compared to the activity of the native ABL1 kinase. The analysis of the protein structure revealed two responsible mechanisms. First, the cap domain, which covers and blocks the catalytic domain in the native...
More than 50 years ago, researchers detected typical chromosomal abnormalities in blood cells of patients with chronic myeloid leukemia (CML). These are an unusually small chromosome 22 and a longer chromosome 9. These mutations were the first genetic alterations regularly linked to a...
The Philadelphia chromosome, which is found in leukemic cells in more than 90% of all patients with chronic myeloid leukemia (CML), results from a translocation between chromosome 9 and chromosome 22. On the Philadelphia chromosome, the 5’ end of the gene BCR is fused to the major 3’ part...
Onkoview 2015
BCR-ABL1 and the Philadelphia chromosome – Part 4: Therapy of tumors with BCR-ABL1 fusion proteins
The specific BCR-ABL1 inhibitor molecule Glivec was the first anti-cancer drug to be developed against a tumor-specific protein. Glivec binds to the catalytic domain of BCR-ABL1 and prevents the binding of the substrate ATP, which is essential for the phosphorylation reaction catalysed by...