biostudies-literatureWendel HGNCI NIH HHS7444-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC1455409biostudies-literatureUnknown103(19)Targeted cancer therapies exploit the continued dependence of cancer cells on oncogenic mutations. Such agents can have remarkable activity against some cancers, although antitumor responses are often heterogeneous, and resistance remains a clinical problem. To gain insight into factors that influence the action of a prototypical targeted drug, we studied the action of imatinib (STI-571, Gleevec) against murine cells and leukemias expressing BCR-ABL, an imatinib target and the initiating oncogene for human chronic myelogenous leukemia (CML). We show that the tumor suppressor p53 is selectively activated by imatinib in BCR-ABL-expressing cells as a result of BCR-ABL kinase inhibition. Inactivation of p53, which can accompany disease progression in human CML, impedes the response to imatinibProceedings of the National Academy of Sciences of the United States of AmericaLoss of p53 impedes the antileukemic response to BCR-ABL inhibition.PMC1455409P01 CA064593P30 CA008748P01 CA087497CA87497Bornmann WGRay SClarkson BLowe SWde Stanchina EHochhaus AFridman JSVeach DRKogan SCEmig MMcCombie WRCepero EWendel HGfalseLoss of p53 impedes the antileukemic response to BCR-ABL inhibition.Targeted cancer therapies exploit the continued dependence of cancer cells on oncogenic mutations. Such agents can have remarkable activity against some cancers, although antitumor responses are often heterogeneous, and resistance remains a clinical problem. To gain insight into factors that influence the action of a prototypical targeted drug, we studied the action of imatinib (STI-571, Gleevec) against murine cells and leukemias expressing BCR-ABL, an imatinib target and the initiating oncogene for human chronic myelogenous leukemia (CML). We show that the tumor suppressor p53 is selectively activated by imatinib in BCR-ABL-expressing cells as a result of BCR-ABL kinase inhibition. Inactivation of p53, which can accompany disease progression in human CML, impedes the response to imatinib2006-01-01T00:00:00Z2006 May2026-03-16T16:20:45.72Z2019-03-27T01:26:22ZS-EPMC14554091665151910.1073/pnas.0602402103