These therapies with covalent and irreversible binding have resulted in prolonged disease-free and overall survival in CLL; however, the persistent presence of drug has resulted in development of drug resistance due to alteration in the BCR pathway, including alteration in the binding site of ibrutinib, i.e., the C481 amino acid of BTK [10–13]. This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.