title: Human B-cell cancer cell lines as a preclinical model for studies of drug effect in diffuse large B-cell lymphoma and multiple myeloma.
abstract: Drug resistance in cancer refers to recurrent or primary refractory disease following drug therapy. At the cellular level, it is a consequence of molecular functions that ultimately enable the cell to resist cell death-one of the classical hallmarks of cancer. Thus, drug resistance is a fundamental aspect of the cancer cell phenotype, in parallel with sustained proliferation, immortality, angiogenesis, invasion, and metastasis. Here we present a preclinical model of human B-cell cancer cell lines used to identify genes involved in specific drug resistance. This process includes a standardized technical setup for specific drug screening, analysis of global gene expression, and the statistical considerations required to develop resistance gene signatures. The state of the art is illustrated by the first-step classical drug screen (including the CD20 antibody rituximab, the DNA intercalating topoisomerase II inhibitor doxorubicin, the mitotic inhibitor vincristine, and the alkylating agents cyclophosphamide and melphalan) along with the generation of gene lists predicting the chemotherapeutic outcome as validated retrospectively in clinical trial datasets. This B-cell lineage-specific preclinical model will allow us to initiate a range of laboratory studies, with focus on specific gene functions involved in molecular resistance mechanisms.
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Maria Bach
authors: MB
authors: Laursen
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Steffen
authors: S
authors: Falgreen
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Julie Støve
authors: JS
authors: Bødker
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Alexander
authors: A
authors: Schmitz
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Malene Krag
authors: MK
authors: Kjeldsen
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Suzette
authors: S
authors: Sørensen
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Jakob
authors: J
authors: Madsen
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors: Tarec Christoffer
authors: TC
authors: El-Galaly
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors: Martin
authors: M
authors: Bøgsted
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors: Karen
authors: K
authors: Dybkær
authors: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: haej@rn.dk.
authors: Hans Erik
authors: HE
authors: Johnsen
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008558:Melphalan / Q000494:pharmacology; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000069283:Rituximab; D014750:Vincristine / Q000494:pharmacology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan