Phospho-Y223 is necessary of full activation of BTK, and hence is a marker of BTK activation.31,32 Furthermore, we also observed that treatment with varying concentrations of the BTK inhibitor ibrutinib, a drug currently prescribed for CLL, significantly reduced p-STAT3-Y705, but not p-STAT3-S727 in JVM-3 cells and three CLL patient cells (Figure 5a(ii) and (iii)).30 CNL did not affect levels of another tyrosine kinase, c-Abl (data not shown). Here, BTK is linked to B-cell chronic lymphocytic leukemia.