DefinitionThis section has been translated automatically.
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The translocation between chromosomes 9 and 22 is characteristic of chronic myeloid leukemia (CML) (Philadelphia chromosome). This leads to the oncogene known as BCR-ABL. This oncogene is a non-receptor tyrosine kinase tyrosine kinase that phosphorylates various substrates. BCR-ABL inhibits the normal proliferation and differentiation of cells.
Imatinib inhibits the intracellularly localized BCR-ABL tyrosine kinase , which is responsible for uncontrolled growth in chronic myeloid leukemia (CML). Imatinib specifically blocks the binding site for ATP at the tyrosine kinase BCR-ABL. This inhibits the transfer of ATP phosphate groups to tyrosine residues of the substrates.
In addition, imatinib also inhibits the c-kit receptor tyrosine kinase (for the growth factor CSF = cytokine stem cell factor", which in mutated form is important for the growth of gastrointestinal stromal cell tumours (GIST).
In addition, the PDGFR (platelet-derived-growth-factor receptor) receptor is inhibited, which plays a role in myelodysplastic/myeloproliferative diseases. If the various tyrosine kinases are listed according to decreasing affinity of the active substances, the tyrosine kinase preference for imatinib is PDGFR > KIT > BCR-ABL, for nilotinib BCR-ABL > PDGFR > KIT.
In this way, signal transduction within cells is prevented. Thus, processes of migration, invasion angiogenesis, proliferation and anti-apoptosis are disturbed.
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IndicationThis section has been translated automatically.
Chronic myeloid leukemia, primary eosinophilia.
Gastrointestinal stromal tumors and myeloproliferative diseases.
Possible applications ( off-label use): dermatofibrosarcoma protuberans; chronic graft-versus-host disease; systemic scleroderma; hypereosinophilia syndrome (off-label use); mastocytosis (off-label use); acrolentiginous malignant melanoma; mucosal melanoma.
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Undesirable effectsThis section has been translated automatically.
autoimmune phenomena and diseases whose management and, if necessary, prophylactic treatment are of great importance. The most frequent side effect is immune-mediated colitis, which, depending on its severity, can also lead to severe, even long-lasting diarrhoea. In addition, other immune-mediated diseases such as hypophysitis, hepatitis, iridocyclitis and the exacerbation of lupus nephritis are also observed.
ContraindicationThis section has been translated automatically.
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LiteratureThis section has been translated automatically.
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- Svegliati S et al (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110: 237-241