title: Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line.
abstract: Immortalized cell lines representative of chronic lymphocytic leukemia (CLL) can assist in understanding disease pathogenesis and testing new therapeutic agents. At present, very few representative cell lines are available. We here describe the characterization of a new cell line (PCL12) that grew spontaneously from the peripheral blood (PB) of a CLL patient with progressive disease and EBV infection. The CLL cell origin of PCL12 was confirmed after the alignment of its IGH sequence against the "original" clonotypic sequence. The IGH gene rearrangement was truly unmutated and no CLL-related cytogenetic or genetic lesions were detected. PCL12 cells express CD19, CD20, CD5, CD23, low levels of IgM and IgD and the poor-outcome-associated prognostic markers CD38, ZAP70 and TCL1. In accordance with its aggressive phenotype the cell line is inactive in terms of LYN and HS1 phosphorylation. BcR signalling pathway is constitutively active and anergic in terms of p-ERK and Calcium flux response to α-IgM stimulation. PCL12 cells strongly migrate in vitro in response to SDF-1 and form clusters. Finally, they grow rapidly and localize in all lymphoid organs when xenotrasplanted in Rag2-/-γc-/- mice. PCL12 represents a suitable preclinical model for testing pharmacological agents.
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy; IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of B Cell Neoplasia, Milano, Italy.
authors.forename: Andreas
authors.initials: A
authors.lastname: Agathangelidis
authors.affiliation: Università Vita-Salute San Raffaele, Milano, Italy; IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of B Cell Neoplasia, Milano, Italy; IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Department of Onco-Hematology, Milan, Italy.
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfò
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barbaglio
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Apollonio
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy; Università Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Maria Teresa Sabrina
authors.initials: MT
authors.lastname: Bertilaccio
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ranghetti
authors.affiliation: IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Department of Onco-Hematology, Milan, Italy; IRCCS San Raffaele Scientific Institute, Pathology Unit, Milan, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Department of Onco-Hematology, Milan, Italy; IRCCS San Raffaele Scientific Institute, Pathology Unit, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leone
authors.affiliation: IRCCS San Raffaele Scientific Institute, Pathology Unit, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Pascali
authors.affiliation: IRCCS San Raffaele Scientific Institute, Pathology Unit, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pecciarini
authors.affiliation: Università Vita-Salute San Raffaele, Milano, Italy; IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of B Cell Neoplasia, Milano, Italy; IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Department of Onco-Hematology, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy; Università Vita-Salute San Raffaele, Milano, Italy; IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Department of Onco-Hematology, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.affiliation: IRCCS San Raffaele Scientific Institute, Division of Experimental Oncology, Unit of Lymphoid Malignancies, Milano, Italy; Università Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scielzo
mesh_terms: D000818:Animals; D018956:CD5 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D015321:Gene Rearrangement; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D018956:CD5 Antigens; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human