Mutations in PLCγ2 and/or Btk have been reported in 11 to 90% cases of Ibrutinib-refractory CLL, further underscoring the importance of better understanding the process by which the partnership of Btk and PLCγ2 drives CLL disease progression (122, 123, 124, 125, 126). This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.