The Importance of Bruton Tyrosine Kinase (BTK) and Targeted Therapies

Submit Manuscript | http://medcraveonline.com (BCR) signalling [6-8], CXCR4 and CXCR5 chemokine receptors, adhesion molecules (integrin), collagen GPVI-FCR gamma chain, GPIB-IX-V complex, CLEC-2 signalling and Toll receptor signalling. BTK is primarily expressed in haematopoietic cells, particularly in B cells, but also in monocytes/macrophages, platelets, neutrophils but not T cells and plasma cells. It is thought that its expression is necessary in the proliferation and survival of B-cells. B-lymphocytes with deficient BTK seem to die at a premature stage. BTK plays a prominent role during B-cell development, as demonstrated in patients with X-Linked Agammaglobulinemia (XLA) who lack peripheral blood B cells and immune globulins [9], thus the humoral immune responses cannot be established [1]. XLA is caused by BTK mutations that result in deficient BTK function. These XLA patients exhibit only a weak platelet aggregation defect in response to low doses of collagen and have no bleeding phenotype [10]. In the mouse model, the Murine BTK gene mutation [8] results in X-Linked Immune Deficiency (XID) which is considered to be milder than XLA although the mutation is the same for both [11]. These differences might be suggestive of species diversity [8,11]. Several BTK inhibitors have been developed. All BTK inhibitors irreversibly target the C481 residue in the kinase domain of BTK, rendering it kinase-inactive, inducing modest Chronic Lymphocytic Leukemia (CLL) cell apoptosis, abolishing proliferation and BCR signalling [12] (Figure 1). Volume 3 Issue 1 2016