Following the engagement of TLR agonists, IRAK4 is recruited to the adaptor protein MYD88 through death-domain interactions and IRAK-4, together with other adaptor proteins such as IRAK2, and MYD88, form a signaling complex, termed the “myddosome.” Many B-cell NHL and myeloid malignancies with spliceosome mutations have augmented myddosomal signaling of which IRAK-4 plays a key role (5, 6). This evidence concerns the gene MYD88 and B-cell non-Hodgkin lymphoma.