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Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia.
Rathe, Susan K; Moriarity, Branden S; Stoltenberg, Christopher B; Kurata, Morito; Aumann, Natalie K; Rahrmann, Eric P; Bailey, Natashay J; Melrose, Ellen G; Beckmann, Dominic A; Liska, Chase R; Largaespada, David A.
Afiliación
  • Rathe SK; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Moriarity BS; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
  • Stoltenberg CB; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Kurata M; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Aumann NK; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Rahrmann EP; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
  • Bailey NJ; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Melrose EG; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Beckmann DA; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [2] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
  • Liska CR; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Largaespada DA; 1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA [4] Brain Tumor Program, University of Minn
Sci Rep ; 4: 6048, 2014 Aug 13.
Article en En | MEDLINE | ID: mdl-25116387
The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and from RNA interference to gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying and quantifying the effects of gene changes on drug resistance. Here we describe the results from deep-sequencing of RNA derived from two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN based methods for accomplishing complete gene knockout (KO) in AML cells. We found protein modifying loss-of-function mutations in Dck in both Ara-C resistant cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC50 of Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted in a significant increase in Ara-C sensitivity. This effort demonstrates the power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and verify genes associated with drug resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteínas Serina-Treonina Quinasas / Resistencia a Antineoplásicos / Citarabina Límite: Animals Idioma: En Revista: Sci Rep Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteínas Serina-Treonina Quinasas / Resistencia a Antineoplásicos / Citarabina Límite: Animals Idioma: En Revista: Sci Rep Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido