TG101209

The germinal center B-cell like diffuse large B-cell lymphoma (DLBCL) cell lines OCI-LY-19 and WSU-DLCL2 were exposed to 348 compounds given as single agents at two different concentrations and in combination with the BET inhibitor birabresib...The screening identified a series of compounds leading to a stronger antiproliferative activity when given in combination than as single agents: the histone deacetylase (HDAC) inhibitors panobinostat and dacinostat, the mTOR (mechanistic target of rapamycin) inhibitor everolimus, the ABL/SRC (ABL proto-oncogene/SRC proto oncogene) inhibitor dasatinib, the AKT1/2/3 inhibitor MK-2206, the JAK2 inhibitor TG101209...Genetic silencing demonstrated that LRRK2 sustains the proliferation of lymphoma cells, a finding paired with the association between high expression levels and inferior outcome in DLBCL patients. We identified combinations that can improve the response to BET inhibitors in lymphomas, and LRRK2 as a gene essential for lymphomas and as putative novel target for this type of tumors.