Abstract
Chronic Myeloid Leukemia (CML) has always been an ideal model to understand the molecular pathogenesis of human leukaemias and the way to cure them. This can be ascribed to the fact that CML was the first human cancer demonstrated to be strongly associated to the presence of a recurrent chromosomal translocation (the t(9;22)(q34;q11) that creates the Philadelphia (Ph)-chromosome) and to a specific molecular defect, the formation of a hybrid BCR-ABL gene that generates new fusion proteins endowed with a constitutive tyrosine-kinase (TK) activity, strongly implicated in the pathogenesis of the disease. The introduction into clinical practice of imatinib, (Glivec, Gleevec, Novartis), a potent tyrosine kinase inhibitor of the Bcr-Abl protein as well as of a restricted number of other TKs, has not only produced a substantial improvement in the treatment of CML, but represents a major break-through in the perspective of opening a new era, that of molecularly targeted therapy, in the management of other types of leukemia, lymphoma and cancer in general.
MeSH terms
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use
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Benzamides
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Bone Marrow Transplantation
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Clinical Trials as Topic
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Drug Monitoring
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Drug Resistance, Neoplasm / physiology
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Fusion Proteins, bcr-abl / antagonists & inhibitors
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism
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Humans
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Imatinib Mesylate
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Interferon-alpha / therapeutic use
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Leukemia / drug therapy
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Leukemia / genetics
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Leukemia / therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
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Philadelphia Chromosome
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Piperazines / administration & dosage
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Piperazines / pharmacokinetics
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Piperazines / therapeutic use*
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Pyrimidines / administration & dosage
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Pyrimidines / pharmacokinetics
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Pyrimidines / therapeutic use*
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Treatment Outcome
Substances
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Antineoplastic Agents
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Benzamides
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Interferon-alpha
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl