Your browser doesn't support javascript.
loading
Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling.
Spirin, P V; Lebedev, T D; Orlova, N N; Gornostaeva, A S; Prokofjeva, M M; Nikitenko, N A; Dmitriev, S E; Buzdin, A A; Borisov, N M; Aliper, A M; Garazha, A V; Rubtsov, P M; Stocking, C; Prassolov, V S.
Afiliación
  • Spirin PV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Lebedev TD; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Orlova NN; 1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia [2] Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
  • Gornostaeva AS; 1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia [2] Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
  • Prokofjeva MM; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Nikitenko NA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Dmitriev SE; 1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia [2] Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
  • Buzdin AA; 1] Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia [2] D Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia [3] Pathway Pharmaceuticals Limited, Wan Chai, Hong Kong Special Administrative Region.
  • Borisov NM; 1] D Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia [2] Pathway Pharmaceuticals Limited, Wan Chai, Hong Kong Special Administrative Region.
  • Aliper AM; 1] Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia [2] D Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
  • Garazha AV; 1] D Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia [2] Pathway Pharmaceuticals Limited, Wan Chai, Hong Kong Special Administrative Region.
  • Rubtsov PM; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Stocking C; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Prassolov VS; 1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia [2] Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
Leukemia ; 28(11): 2222-8, 2014 Nov.
Article en En | MEDLINE | ID: mdl-24727677
The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Transducción de Señal / Regulación Leucémica de la Expresión Génica / Proteínas de Fusión Oncogénica / Apoptosis / Proteínas Proto-Oncogénicas c-kit / Subunidad alfa 2 del Factor de Unión al Sitio Principal Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2014 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Transducción de Señal / Regulación Leucémica de la Expresión Génica / Proteínas de Fusión Oncogénica / Apoptosis / Proteínas Proto-Oncogénicas c-kit / Subunidad alfa 2 del Factor de Unión al Sitio Principal Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2014 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Reino Unido