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Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance.
Jack, J; Small, G W; Brown, C C; Havener, T M; McLeod, H L; Motsinger-Reif, A A; Richards, K L.
Afiliación
  • Jack J; Department of Statistics, North Carolina State University, Raleigh, NC, USA.
  • Small GW; Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
  • Brown CC; Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Havener TM; Q2 Solutions - EA Genomics, A Quintiles Quest Joint Venture, Morrisville, NC, USA.
  • McLeod HL; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.
  • Motsinger-Reif AA; DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, Florida, USA.
  • Richards KL; Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Pharmacogenomics J ; 18(3): 467-473, 2018 05 22.
Article en En | MEDLINE | ID: mdl-29205205
Elucidating resistance mechanisms for therapeutic monoclonal antibodies (MAbs) is challenging, because they are difficult to study in non-human models. We therefore developed a strategy to genetically map in vitro drug sensitivity, identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20 MAb that provides significant benefit to patients with B-cell malignancies. We discovered novel loci with genome-wide mapping analyses and functionally validated one of these genes, CBLB, which causes rituximab resistance when knocked down in lymphoma cells. This study demonstrates the utility of genome-wide mapping to discover novel biological mechanisms of potential clinical advantage.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Resistencia a Antineoplásicos / Proteínas Adaptadoras Transductoras de Señales / Proteínas Proto-Oncogénicas c-cbl / Rituximab Límite: Female / Humans / Male Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Resistencia a Antineoplásicos / Proteínas Adaptadoras Transductoras de Señales / Proteínas Proto-Oncogénicas c-cbl / Rituximab Límite: Female / Humans / Male Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos