The BLIMP1 - EZH2 nexus in a non-Hodgkin lymphoma

Waldenstrom9s macroglobulinemia (WM) is a non-Hodgkin lymphoma, affecting antibody-secreting lymphoplasmacytic cells in the bone marrow. BLIMP1 is a key transcriptional repressor which drives the transition from B cells to plasma cells and is essential for antibody secretion. Despite this, a potential role for BLIMP1 in WM has not yet been explored. Here we provide evidence of a crucial role for BLIMP1 in the survival of WM cells. We further demonstrate that BLIMP1 is necessary for the expression of the histone methyltransferase EZH2 in both WM and multiple myeloma, most likely through a regulation of proteasomal targeting of EZH2. Chromatin immunoprecipitation analysis and genome wide transcriptome profiling show that the two factors co-operate in regulating genes involved in cancer cell immune evasion. Co-cultures of natural killer cells and WM cells further reveal that both factors participate directly in immune evasion, promoting escape from natural killer cell mediated cytotoxicity. Together, the interplay of BLIMP1 and EZH2 plays a vital role in promoting the survival of WM cells.