In addition, we demonstrate that the MYD88 S257D mutant, which mimics constitutive S257 phosphorylation, induces strong MYD88 aggregation, IRAK1 phosphorylation, NF- κB activity and proliferation in DLBCL cells, similar to the L265P mutant, and, moreover, rescues lymphoma cells addicted to MYD88 L265P upon silencing of this oncogene. Here, IRAK1 is linked to diffuse large B-cell lymphoma.