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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-06-1668. This Article Full Text (PDF) All Versions of this Article: 2002-06-1668v1 101/1/202    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pistillo, M. P. Articles by Ferrara, G. B. Search for Related Content PubMed PubMed Citation Articles by Pistillo, M. P. Articles by Ferrara, G. B. Social Bookmarking                   What's this? Submitted June 6, 2002 Accepted August 5, 2002 CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells Maria Pia Pistillo*, Pier Luigi Tazzari, Giulio Lelio Palmisano, Ivana Pierri, Andrea Bolognesi, Francesca Ferlito, Paolo Capanni, Letizia Polito, Marina Ratta, Stefano Pileri, Milena Piccioli, Giuseppe Basso, Laura Rissotto, Roberto Conte, Marco Gobbi, Fiorenzo Stirpe, and Giovanni Battista Ferrara Immunogenetics, National Cancer Research Institute, Genova, Italy Service of Transfusion Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy Molecular Morphogenesis, National Cancer Research Institute, Genova, Italy Department of Internal Medicine, University of Genova, Genova, Italy Department of Experimental Pathology, University of Bologna, Bologna, Italy Hemolymphopathology Section, University of Bologna, Institute of Hematology and Clinical Oncology L.& A. Seragnoli, Bologna, Italy Department of Pediatrics, University of Padova Medical School, Padova, Italy Immunogenetics, National Cancer Research Institute, Genova, Italy; Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy * Corresponding author; email: mariapia.pistillo{at}istge.it. The expression of CTLA-4 molecule in human normal and neoplastic hematopoietic cells both on the cell membrane and in the intracellular compartment was evaluated. Flow cytometric analysis carried out with a panel of anti-CTLA-4 human scFv antibodies revealed that CTLA-4 was not expressed on the surface, whereas it was highly expressed within the cytoplasm, in freshly isolated PBMCs, T cells, B cells, CD34+ stem cells and granulocytes. Various treatments with agents able to specifically activate each cell type induced CTLA-4 expression on surface of these cells. Similarly, increased CTLA-4 expression was observed in different hematopoietic cell lines although they expressed surface CTLA-4, at different degrees of intensity, also before activation. Surprisingly, CTLA-4 RNA transcripts were detectable in such cell lines only after nested PCR specific for CTLA-4 extracellular domain, suggesting a very fast CTLA-4 RNA processing accompanied by prolonged CTLA-4 protein accumulation. We further demonstrated surface expression of CTLA-4 in a variety of acute and chronic myeloid (AML and CML) leukemias and B- and T-lymphoid leukemias either adult or pediatric. CTLA-4 was expressed in 25% to 85% of AML and CML depending on the leukemia subtype and the epitope analyzed, whereas in acute B- and T-leukemias CTLA-4 expression was mainly cytoplasmic. Chronic B-leukemias appeared to express CTLA-4 both on surface and in cytoplasm, while few cases tested of chronic T-leukemias were negative. Two anti-CTLA-4 immunotoxins (scFvs-saporin) induced in vitro apoptosis of neoplastic cells from a representative AML suggesting a novel immunotherapeutic approach of AML based on CTLA-4 targeting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. R. Daniels, P. P. Ng, T. Delgado, M. R. Lynch, G. Schiller, G. Helguera, and M. L. Penichet Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells Mol. Cancer Ther., November 1, 2007; 6(11): 2995 - 3008. [Abstract] [Full Text] [PDF]

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