engleski

AMN107, a Novel Aminopyrimidine Inhibitor of p190 Bcr-Abl Activation and of In Vitro Proliferation of Philadelphia– Positive Acute Lymphoblastic Leukemia Cells.

Background. Patients with Bcr-Abl positive acute lymphoblastic leukemia (ALL) are either primary refractory to imatinib mesylate or relapse after an initial response. Methods. We investigated the effects of a newly designed Bcr-Abl inhibitor, AMN107, by comparing its in vitro inhibitory potency on p190-Bcr-Abl ALL cell lines with that of imatinib. Results. In two Ph-positive ALL cell lines, AMN107 was 30-40 times more potent than imatinib in inhibiting cellular proliferation. AMN107 was also more effective than imatinib in inhibiting phosphorylation of p190 Bcr-Abl tyrosine kinase in cell lines and primary ALL cells. The inhibition of cellular proliferation was associated with induction of apoptosis in only one of the cell lines. No activity was observed in cell lines lacking BCR-ABL genotype. Conclusions. Our results suggest the superior potency of AMN107 over imatinib in Ph-positive ALL and support clinical trials of AMN107 in patients with Ph-positive ALL.

Bcr-Abl kinase inhibitor; AMN107; imatinib; acute lymphoblastic leukemia; in vitro models

nije evidentirano