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A role for dystroglycan in the pathophysiology of acute leukemic cells.
Alonso-Rangel, Lea; Benítez-Guerrero, Tizziani; Martínez-Vieyra, Ivette; Cisneros, Bulmaro; Martínez-Tovar, Adolfo; Winder, Steve J; Cerecedo, Doris.
Afiliação
  • Alonso-Rangel L; Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
  • Benítez-Guerrero T; Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
  • Martínez-Vieyra I; Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
  • Cisneros B; Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav-IPN), Mexico City, Mexico.
  • Martínez-Tovar A; Servicio de Hematología, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico.
  • Winder SJ; Department of Biomedical Science, University of Sheffield, Sheffield, UK.
  • Cerecedo D; Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), Mexico City, Mexico. Electronic address: dcereced@prodigy.net.mx.
Life Sci ; 182: 1-9, 2017 Aug 01.
Article em En | MEDLINE | ID: mdl-28591567
AIMS: Previous reports have demonstrated that alterations or reduced expression of Dystroglycan (Dg) complex (αDg and ßDg subunits) are related to progression and severity of neoplastic solid tissues. Therefore we determined the expression pattern and subcellular distribution of Dg complex in Acute Myeloid Leukemia (AML) primary blasts (M1, M2, and M3 phenotypes), as well as HL-60 and Kasumi-1 leukemia cell lines. Additionally, we evaluated the relative expression of the main enzymes controlling α-Dg glycosylation to ascertain the post-translational modifications in the leukemia cell phenotype. MAIN METHODS: Primary leukemia blasts and leukemia cell lines were processed by confocal analysis to determine the subcellular distribution of α-Dg, ß-Dg, and phosphorylated ß-Dg (Y892), to evaluate the expression pattern of the different Dg species we performed Western Blot (WB) assays, while the messenger RNA (mRNA) expression of enzymes involved in α-Dg glycosylation, such as POMGnT1, POMT1, POMT2, LARGE, FKTN, and FKRP, were evaluated by qualitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Finally, in an attempt to ameliorate the leukemia cell phenotype, we transfected leukemia cells with a plasmid expressing the Dg complex. KEY FINDINGS: The Dg complex was altered in leukemia cells, including decreased mRNA, protein, and α-Dg glycosylated levels, mislocalization of ß-Dg, and a diminution of mRNA expression of LARGE in patients leukemia blasts and in cell lines. Interestingly, the exogenous expression of Dg complex promoted filopodial formation, differentiation, and diminished proliferation, attenuating some HL-60 and Kasumi cells characteristics. SIGNIFICANCE: Dg complex integrity and balance are required for a proper hematopoietic cell function, in that its disruption might contribute to leukemia pathophysiology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Regulação Neoplásica da Expressão Gênica / Processamento de Proteína Pós-Traducional / Distroglicanas Tipo de estudo: Qualitative_research Limite: Humans Idioma: En Revista: Life Sci Ano de publicação: 2017 Tipo de documento: Article País de afiliação: México País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Regulação Neoplásica da Expressão Gênica / Processamento de Proteína Pós-Traducional / Distroglicanas Tipo de estudo: Qualitative_research Limite: Humans Idioma: En Revista: Life Sci Ano de publicação: 2017 Tipo de documento: Article País de afiliação: México País de publicação: Holanda