title: Diffuse Large B Cell Lymphoma Cell Line U-2946: Model for MCL1 Inhibitor Testing.
abstract: Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n). MCL1 amplification is recurrent in DLBCL, especially in the activated B cell (ABC) variant. Results of microarray expression cluster analysis placed U-2946 together with ABC-, but apart from germinal center (GC)-type DLBCL cell lines. The 1q21.3 region including MCL1 was focally coamplified with a short region of 17p11.2 (also present at 14n). The MCL1 inhibitor A-1210477 triggered apoptosis in U-2946 (MCL1pos/BCL2neg) cells. In contrast to BCL2pos DLBCL cell lines, U-2946 did not respond to the BCL2 inhibitor ABT-263. In conclusion, the novel characteristics of cell line U-2946 renders it a unique model system to test the function of small molecule inhibitors, especially when constructing a panel of DLBCL cell lines expressing broad combinations of antiapoptotic BCL2-family members.
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Quentmeier
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Drexler
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Vivien
authors.initials: V
authors.lastname: Hauer
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Roderick A F
authors.initials: RA
authors.lastname: MacLeod
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pommerenke
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Cord C
authors.initials: CC
authors.lastname: Uphoff
authors.affiliation: Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Margarete
authors.initials: M
authors.lastname: Zaborski
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Berglund
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D000814:Aniline Compounds; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C528561:navitoclax