Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress 
T-cell activation and proliferation. We report a series of 8 patients who 
developed chronic peripheral lymphocytosis, identified as natural killer cells 
or natural killer/T-cells based on their large granular lymphocyte morphologies 
and CD16(+), CD56(+), CD3(-) or CD3(+) immunophenotypic profiles, out of 18 
patients receiving dasatinib therapy. All cases that developed large granular 
lymphocyte lymphocytosis achieved optimal molecular response (8/8 in large 
granular lymphocyte(+) patients vs. 3/10 in large granular lymphocyte(-) 
patients, p=0.002). A (51)Cr release assay demonstrated that natural killer cell 
cytotoxicity has been enhanced in a case of large granular lymphocyte 
lymphocytosis compared to normal healthy donors, and that natural killer cell 
cytotoxicity in dasatinib-responders was superior to that in non-responders. In 
summary, the present study suggests that natural killer or natural killer/T cell 
lineage large granular lymphocyte lymphocytosis develops in association with 
dasatinib therapy and that large granular lymphocyte might have a therapeutic 
effect on Ph(+) leukemic cells.