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Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia.
Raponi, Mitch; Harousseau, Jean-Luc; Lancet, Jeffrey E; Löwenberg, Bob; Stone, Richard; Zhang, Yi; Rackoff, Wayne; Wang, Yixin; Atkins, David.
Afiliación
  • Raponi M; Veridex, L.L.C. a Johnson & Johnson Company, San Diego, California 92121, USA. mraponi1@vrxus.jnj.com
Clin Cancer Res ; 13(7): 2254-60, 2007 Apr 01.
Article en En | MEDLINE | ID: mdl-17404110
ABSTRACT

PURPOSE:

Microarray technology was used to identify gene expression markers that predict response to the orally available farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in acute myelogenous leukemia (AML). EXPERIMENTAL

DESIGN:

Gene expression profiles from 58 bone marrow samples from a cohort of relapsed and refractory AML patients were analyzed on the Affymetrix U133A gene chip that contains approximately 22,000 genes.

RESULTS:

Supervised statistical analysis identified eight gene expression markers that could predict patient response to tipifarnib. The most robust gene was the lymphoid blast crisis oncogene (AKAP13), which predicted response with an overall accuracy of 63%. This gene provided a negative predictive value of 93% and a positive predictive value of 31% (increased from 18%). AKAP13 was overexpressed in patients who were resistant to tipifarnib. When overexpressed in the HL60 and THP1 cell lines, AKAP13 increased the resistance to tipifarnib by approximately 5- to 7-fold.

CONCLUSION:

Diagnostic gene expression signatures may be used to select a group of AML patients that might respond to tipifarnib.
Asunto(s)
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Biomarcadores de Tumor / Quinolonas / Resistencia a Antineoplásicos / Recurrencia Local de Neoplasia / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Biomarcadores de Tumor / Quinolonas / Resistencia a Antineoplásicos / Recurrencia Local de Neoplasia / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos