Diffuse Large B Cell Lymphoma Cell Line U2946 Model for MCL1 Inhibitor Testing

• Published in: PloS one Vol. 11; no. 12
• Main Authors: Quentmeier, Hilmar, Drexler, Hans G., Hauer, Vivien, MacLeod, Roderick A. F., Pommerenke, Claudia, Uphoff, Cord C., Zaborski, Margarete, Berglund, Mattias, Enblad, Gunilla, Amini, Rose-Marie
• Format: Journal Article
• Language: English
• Published: 01.12.2016
• Subjects: Pathology; Patologi
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167599

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.