In the work presented here, we provide compelling data that SLAMF1 and SLAMF7 receptors may not only enhance immune control of CLL but also negatively regulate BCR signaling and thereby impact sensitivity towards BTK inhibition in the substantial fraction of patients with SLAMF1 or SLAMF7 expressing M-CLL. The gene discussed is SLAMF1; the disease is B-cell chronic lymphocytic leukemia.