[Chronic myeloid leukemia as a model for modern noncytostatic therapy of malignant diseases. From Virchow to STI 571].
Chronic myelogenous leukemia (CML) has been described in the middle of the 19th century. It took further 100 years to the time of the discovery of the first cytotoxic drugs. Ph1 chromosome, the cytogenetic hallmark of CML, has been described in 1960, however, the majority of important discoveries on the molecular level has been done in the 1980s' and later. The chromosomal translocation t(9;22)(q34;q11) is absolutely crucial for CML and leads to the chimeric gene and protein BCR-ABL. The ABL protein possesses the tyrosine kinase activity, which is deregulated in the BCR-ABL protein, leading to the cascade of further pathological processes in the leukemic cells and causing eventually their malignant transformation. In the 1990s, the drug STI 571 has been synthesized, which is a potent inhibitor of the ABL tyrosine kinase activity. The data so far published concerning clinical effects of STI 571 are remarkable and very encouraging. The drug seems to be very safe and has only limited toxicity. It must be emphasized, however, that STI 571 has been clinically tested only since 1998. Moreover, from the mechanisms of action it is clear, that STI 571 influences the secondary, not the primary cause of the CML. Nevertheless, it is without any doubts that the development of new anti-cancer drugs will be done on this non-cytotoxic principle.
Mayer
J
J
Interní hematoonkologická klinika Fakultní nemocnice Brno, pracovistĕ Bohunice.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl