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- Bcr-Abl_tyrosine-kinase_inhibitor abstract "Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). In more than 90% cases CML is caused by chromosomal abnormality resulting in the formation of a so-called Philadelphia chromosome. This abnormality was discovered by Janet Rowley in 1972 and is due to fusion between Abelson (Abl) tyrosine kinase gene at chromosome 9 and break point cluster (Bcr) gene at chromosome 22, resulting in the chimeric oncogene Bcr-Abl and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML. Compounds have been developed that selectively inhibit this tyrosine kinase. Before the U.S. Food and Drug Administration (FDA) approval of imatinib in 2001 no drugs were used that changed the natural progression of CML, only cytotoxic drugs such as busulfan, hydroxyurea or interferon-alpha (rIFN-α). Even though the first Bcr-Abl TK inhibitor was named “the magic bullet” to cure cancer by TIME magazine, a second generation of Bcr-Abl TKI has been developed as a cause of resistance to imatinib emerged. New forms of resistance in patients can arise as; missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or constitutive activating of downstream signaling molecules such as Src-family kinases. Most of the drugs are adenosine triphosphate (ATP)-competitive inhibitors.".
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- Bcr-Abl_tyrosine-kinase_inhibitor subject Category:Drug_discovery.
- Bcr-Abl_tyrosine-kinase_inhibitor subject Category:Leukemia.
- Bcr-Abl_tyrosine-kinase_inhibitor subject Category:Medical_treatments.
- Bcr-Abl_tyrosine-kinase_inhibitor subject Category:Non-receptor_tyrosine_kinase_inhibitors.
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- Bcr-Abl_tyrosine-kinase_inhibitor comment "Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). In more than 90% cases CML is caused by chromosomal abnormality resulting in the formation of a so-called Philadelphia chromosome.".
- Bcr-Abl_tyrosine-kinase_inhibitor label "Bcr-Abl tyrosine-kinase inhibitor".
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