Journal Article

Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Lozanski, Gerard, Rassenti, Laura, Towns, William H., Senter, Leigha, Symer, David E., Heerema, Nyla A., Lozanski, Arletta, Chen, Timothy L., Hertlein, Erin, Bolon, Brad, Byrd, John C., Johnson, Amy J., Jarvinen, Tiina M., Croce, Carlo M., Andritsos, Leslie, Beckwith, Kyle A., Lehman, Amy, de la Chapelle, Albert, Ruppert, Amy S., Zhao, Weiqiang

2013

Overview

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient's CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient's normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animal models / Animals / Apoptosis / B cells / Biotechnology / Bone marrow / Bone marrow transplantation / Cancer / Cancer research / CD5 antigen / Cell Culture Techniques / Cell Line, Tumor / Cell migration / Cell Movement / Cell Transformation, Viral / Chemokines / Chromosomes / Chronic lymphocytic leukemia / Development and progression / DNA microarrays / Gene expression / Genes / Genetic transformation / Genetics / Health risk assessment / Hematology / Herpesvirus 4, Human - physiology / Humans / Immunology / In vivo methods and tests / Internal medicine / Kinases / Leukemia / Leukemia, Lymphocytic, Chronic, B-Cell - genetics / Leukemia, Lymphocytic, Chronic, B-Cell - pathology / Lymphatic leukemia / Lymphocyte receptors / Lymphocytes B / Medical treatment / Medicine / Mice / Mutation / Pathogenesis / Pathology / Peripheral blood / Phenotype / Spleen / Transformation / Trisomy / Virology