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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.

Diffuse Large B Cell Lymphoma Cell Line U-2946: Model for MCL1 Inhibitor Testing