Several BCR-targeted agents, including inhibitors of BTK (ibrutinib), PI3Kδ (idelalisib) and SYK (R406/fostamatinib) have demonstrated not only promising preclinical activities [9–18] but also remarkable clinical efficacy against CLL in large clinical trials [19–23]. The gene discussed is SYK; the disease is B-cell chronic lymphocytic leukemia.