The central role of BTK in B-cell malignancies was first discovered by Davis et al., through RNA interference genetic screen in human lymphoma cell lines, demonstrating that BTK is essential for the survival of the activated B-cell-like (ABC) a subtype of diffuse large B-cell lymphoma (DLBCL) addicted to the NF-κΒ pathway [20]. Here, BTK is linked to diffuse large B-cell lymphoma.