Alternative BCR/ABL splice variants in Philadelphia chromosome-positive Leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches (Articolo in rivista)

Type
Label
  • Alternative BCR/ABL splice variants in Philadelphia chromosome-positive Leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1158/0008-5472.CAN-06-3737 (literal)
Alternative label
  • Volpe G.1; Cignetti A3; Panuzzo C.1; Kuka M.1; Vitaggio K.3; Brancaccio M.2; Perrone G.6; Rinaldi M.8; Prato G.4; Fava M.1; Geuna M.4; Pautasso M.5; Casnici C.9; Signori E.7,8,10; Tonon G.11; Tarone G.2; Marelli O.9; Fazio V.M.7,10; Saglio G.1 (2007)
    Alternative BCR/ABL splice variants in Philadelphia chromosome-positive Leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches
    in Cancer research (Chic. Ill.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Volpe G.1; Cignetti A3; Panuzzo C.1; Kuka M.1; Vitaggio K.3; Brancaccio M.2; Perrone G.6; Rinaldi M.8; Prato G.4; Fava M.1; Geuna M.4; Pautasso M.5; Casnici C.9; Signori E.7,8,10; Tonon G.11; Tarone G.2; Marelli O.9; Fazio V.M.7,10; Saglio G.1 (literal)
Pagina inizio
  • 5300 (literal)
Pagina fine
  • 5307 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • KeyWords Plus: CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; IMATINIB MESYLATE TREATMENT; BCR-ABL; RESIDUAL-DISEASE; FLOW-CYTOMETRY; MOLECULAR RESPONSE; INTERFERON-ALPHA; T-LYMPHOCYTES Publisher: AMER ASSOC CANCER RESEARCH, 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA Web of Science Category: Oncology Subject Category: Oncology IDS Number: 175NS ISSN: 0008-5472 Times Cited: 17 (from Web of Science) 2010 Impact Factor: 8.234 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 67 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1 Departments of Clinical and Biological Sciences and 2 Genetics, Biology and Biochemistry, University of Turin; 3 Laboratories of Tumor Immunology and 4 Clinical and Experimental Cytometry, Institute for Cancer Research and Treatment, Candiolo; 5 Department of Pathology, San Luigi Hospital, Turin, Italy; 6 Laboratory of Hystopathology and 7 Interdisciplinary Center for Biomedical Research, Section of Molecular Medicine and Biotechnology, University Campus Bio-Medico; 8 National Research Council, Institute of Neurobiology and Molecular Medicine, Laboratory of Gene Medicine, Area of Rome Tor Vergata, Rome, Italy; 9 Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy; 10 U.O. Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 11 Bio-Ker, Polaris Scientific Park, Piscinamanna-Pula (Cagliari), Italy (literal)
Titolo
  • Alternative BCR/ABL splice variants in Philadelphia chromosome-positive Leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches (literal)
Abstract
  • Imatinib currently represents the standard treatment in the early chronic phase of chronic myelogenous leukemia (CML), thanks to the high percentage of cytogenetic complete remission achieved, but it is yet unclear to what extent it can eradicate leukemia. Therefore, different vaccination strategies have been suggested, mainly based on the exploitment of the junctional peptides spanning the fusion region of the Bcr/Abl proteins. To identify new potential immunologic targets, 63 Philadelphia chromosome–positive patients and 6 BCR/ABL–positive cell lines were tested in nested reverse transcriptase PCR to detect the presence of BCR/ABL transcripts arising from the alternative splicing of the main BCR/ABL transcripts. We could detect BCR/ABL transcripts with junctions between BCR exon 1, 13, or 14 and ABL exon 4 in 80% of patients and 84% of cell lines, beside the main fusion transcripts. Translation products of these transcripts were characterized at their COOH terminus by a large amino acid portion derived from the out of frame (OOF) reading of ABL gene. These proteins were detected in BCR/ABL–positive cell lines by immunoprecipitation and immunohistochemistry. Finally, we determined whether OOF-specific CD8+ T cells could be found in the peripheral blood of CML patients and whether they could acquire effector function following in vitro sensitization with OOF-derived peptides predicted to bind to human leucocyte antigen (HLA)-A2 and HLA-A3 molecules. We detected the presence of OOF-specific CD8+ T cells in four of four patients studied, and in one case, these T cells exhibited specific cytotoxic activity against both peptide-pulsed targets and autologous primary CML cells. (literal)
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