Status of bcr-abl tyrosine kinase inhibitors in chronic myelogenous leukemia.
The bcr-abl fusion protein is present in the vast majority of cases of chronic myelogenous leukemia, and the deregulated tyrosine kinase activity of this protein is essential for leukemic transformation. Thus, bcr-abl is an ideal target for pharmacologic inhibition. In preclinical studies, ST1571 (formerly CGP57148B), an abl-specific, tyrosine kinase inhibitor, selectively killed bcr-abl-expressing cells both in vitro and in vivo. In early clinical trials of ST1571, encouraging results have been obtained, and there is already a suggestion that ST1571 may soon need to be incorporated into treatment algorithms for chronic myelogenous leukemia.
O'Dwyer
M E
ME
Leukemia Program, Oregon Health Sciences University, Portland 97201, USA.
Druker
B J
BJ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001549:Benzamides; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism*; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl