Mechanisms of resistance to sti571 in philadelphia chromosome-associated leukemias

ABSTRACT Philadelphia chromosome-associated leukemias are among the most well-understood human malignancies. The importance of BCR-ABL enzymatic activity in the proliferation of the leukemic

clone has been confirmed by the high response rates of these leukemias to the _ABL_-selective tyrosine kinase inhibitor STI571, even in advanced disease phases, which are characterized by

increased genetic heterogeneity. Disease relapse has been observed in a subset of patients who had initially responded to STI571. Evidence suggests that BCR-ABL activity is restored in the

majority of these cases of acquired resistance. Molecular studies of resistant leukemia cells isolated from patients have implicated _BCR-ABL_ kinase domain point mutation as the most common

mechanism of resistance. Additionally, genomic amplification of the _BCR-ABL_ gene can occasionally be detected. This review will highlight mechanisms of STI571 resistance in clinical

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Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS COMBINED INHIBITION OF XIAP AND BCL2 DRIVES MAXIMAL THERAPEUTIC EFFICACY IN GENETICALLY DIVERSE AGGRESSIVE

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assistance with manuscript preparation. NPS and CLS are supported by awards from the Leukemia and Lymphoma Society. CLS is a Doris Duke Distinguished Clinical Scientist. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, 90095, CA, USA Neil P Shah & Charles L Sawyers *

Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, 90095, CA, USA Charles L Sawyers * Department of Urology, David Geffen

School of Medicine, University of California, Los Angeles, Los Angeles, 90095, CA, USA Charles L Sawyers * Department of Medical and Molecular Pharmacology, David Geffen School of Medicine,

University of California, Los Angeles, Los Angeles, 90095, CA, USA Charles L Sawyers Authors * Neil P Shah View author publications You can also search for this author inPubMed Google

Scholar * Charles L Sawyers View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Charles L Sawyers. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shah, N., Sawyers, C. Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. _Oncogene_

22, 7389–7395 (2003). https://doi.org/10.1038/sj.onc.1206942 Download citation * Published: 23 October 2003 * Issue Date: 20 October 2003 * DOI: https://doi.org/10.1038/sj.onc.1206942 SHARE

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clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * tyrosine kinase inhibitor * BCR-ABL * imatinib * gleevec * mutation