title: Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8.
abstract: Subset #8 is a distinctive subset of patients with chronic lymphocytic leukemia (CLL) defined by the expression of stereotyped IGHV4-39/IGKV1(D)-39 B-cell receptors. Subset #8 patients experience aggressive disease and exhibit the highest risk for Richter transformation among all CLL. In order to obtain biological insight into this behavior, we profiled the antigen reactivity and signaling capacity of subset #8 vs other clinically aggressive stereotyped subsets, namely subsets #1 and #2. Twenty-seven monoclonal antibodies (mAbs) from subsets #1, #2, and #8 CLL clones were prepared as recombinant human immunoglobulin G1 and used as primary antibodies in enzyme-linked immunosorbent assays against representatives of the major classes of established antigenic targets for CLL. Subset #8 CLL mAbs exhibited broad polyreactivity as they bound to all antigens tested, in clear contrast with the mAbs from the other subsets. Antigen challenge of primary CLL cells indicated that the promiscuous antigen-binding activity of subset #8 mAbs could lead to significant cell activation, again in contrast to the less responsive CLL cells from subsets #1 and #2. These features constitute a distinctive profile for CLL subset #8, supporting the existence of distinct mechanisms of aggressiveness in different immunogenetic subsets of CLL.
authors.affiliation: Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Department of Onco-Hematology, Ospedale San Raffaele, Milan, Italy;
authors.forename: Maria
authors.initials: M
authors.lastname: Gounari
authors.affiliation: Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece;
authors.forename: Stavroula
authors.initials: S
authors.lastname: Ntoufa
authors.affiliation: Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Department of Onco-Hematology, Ospedale San Raffaele, Milan, Italy; Section of Internal Medicine, Università Vita-Salute San Raffaele, and.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Apollonio
authors.affiliation: Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece;
authors.forename: Nikos
authors.initials: N
authors.lastname: Papakonstantinou
authors.affiliation: Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Department of Onco-Hematology, Ospedale San Raffaele, Milan, Italy; Section of Internal Medicine, Università Vita-Salute San Raffaele, and Pathology Unit, IRCCS Istituto Scientifico San Raffaele, Milan, Italy;
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chu
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; and.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; and.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
authors.affiliation: Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.affiliation: Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Department of Onco-Hematology, Ospedale San Raffaele, Milan, Italy; Section of Internal Medicine, Università Vita-Salute San Raffaele, and.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology*; D008297:Male
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm