title: FAS system deregulation in T-cell lymphoblastic lymphoma.
abstract: The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations.
authors.affiliation: 1] Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain [2] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain [3] Instituto de Investigación Sanitario Fundación Jiménez Díaz, ISCIII, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Villa-Morales
authors.affiliation: 1] Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain [2] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain [3] Instituto de Investigación Sanitario Fundación Jiménez Díaz, ISCIII, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Cobos
authors.affiliation: Musculoskeletal Research Center, NYU Hospital for Joint Diseases, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: González-Gugel
authors.affiliation: Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Álvarez-Iglesias
authors.affiliation: 1] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain [2] Instituto de Investigación de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Martínez
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Fundación IFIMAV, Santander, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
authors.affiliation: 1] Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Santiago de Compostela, Spain [2] Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, KSA.
authors.forename: A
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: 1] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain [2] Human Genetics Group, CNIO, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Benítez
authors.affiliation: 1] Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain [2] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain [3] Instituto de Investigación Sanitario Fundación Jiménez Díaz, ISCIII, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Piqueras
mesh_terms: D017209:Apoptosis; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor