Natural Killer (NK) or NK/T Cell Lineage Large Granular Lymphocytosis Associated with Dasatinib Therapy for Philadelphia Chromosome Positive Leukemia.

Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress T-cell activation and proliferation. We report a series of patients of chronic peripheral lymphocytosis development, identified as natural killer (NK) cells or NK/T-cells based on their large granular lymphocyte (LGL) morphologies and CD16⁺CD56⁺CD3⁻ or CD3⁺ immunophenotypic profiles during dasatinib therapy. All cases that developed LGL lymphocytosis achieved optimal molecular response (8/8 in LGL⁺ patients vs 3/10 in LGL⁻ patients, p=0.002). A ⁵¹Cr release assay demonstrated that NK cell cytotoxicity has been enhanced in a case of LGL lymphocytosis compared to normal healthy donors (Figure 1), and that NK cell cytotoxicity in dasatinib-responders was superior to that in non-responders (Figure 2). In summary, the present study suggests that NK or NK/T cell lineage LGL lymphocytosis develops associated with dasatinib therapy and that LGL might have a therapeutic effect on Ph⁺ leukemic cells.

Figure 1.

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Cytotoxicity of NK cells isolated from the patients developing large granular lymphocytosis following dasatinib therapy as assessed by ⁵¹Cr release assays using target cells as K562 (A) and T2 cell line (B) as target cells.

Figure 1.

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Cytotoxicity of NK cells isolated from the patients developing large granular lymphocytosis following dasatinib therapy as assessed by ⁵¹Cr release assays using target cells as K562 (A) and T2 cell line (B) as target cells.

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Figure 2.

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The result of ⁵¹Cr release assays comparing cytotoxicity of NK cells isolated from patients responding to dasatinib therapy (responder) and not responding (non-responder) following dasatinib therapy using K562 cell line as target cells.

Figure 2.

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The result of ⁵¹Cr release assays comparing cytotoxicity of NK cells isolated from patients responding to dasatinib therapy (responder) and not responding (non-responder) following dasatinib therapy using K562 cell line as target cells.

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