STI571 as a targeted therapy for CML.
Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases as the malignant clone progressively loses the capacity for terminal differentiation. It is characterized by the (9;22) translocation and resultant production of the Bcr-Abl tyrosine kinase. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. In preclinical studies, STI571 (Gleevec, imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor, specifically inhibited the proliferation of Bcr-Abl-expressing cells in vitro and in vivo. STI571 has shown remarkable results in all phases of CML. Although responses are seen in all phases of the disease, durable responses are most common in earlier stage patients. Thus, STI571 has emerged as a paradigm for gene product targeted therapy, offering expanded treatment options for patients with CML.
O'Dwyer
Michael E
ME
Leukemia Center, Oregon Health & Science University Cancer Institute, Portland, Oregon, USA.
Mauro
Michael J
MJ
Druker
Brian J
BJ
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl