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Diffuse Large B Cell Lymphoma Cell Line U2946: Model for MCL1 Inhibitor Testing
Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0167599Article in journal (Refereed) Published
Abstract [en]

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 (MCL1(pos)/BCL2(neg)) cells. In contrast to BCL2(pos) 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.

Place, publisher, year, edition, pages
2016. Vol. 11, no 12, article id e0167599
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-312657DOI: 10.1371/journal.pone.0167599ISI: 000389482700210OAI: oai:DiVA.org:uu-312657DiVA, id: diva2:1064625
Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2017-11-29Bibliographically approved

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Berglund, MattiasEnblad, GunillaAmini, Rose-Marie
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