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 51Cr 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.

Genome-wide DNA copy number analysis by SNP arrays of B-cell chronic lymphocytic leukemia reveals the presence of novel molecular lesions / L. Mosca, L. Agnelli, S. Fabris, G. Cutrona, S. Matis, M. Lionetti, K. Todoerti, A. Andronache, M. Gentile, M. Spriano, V. Callea, G. Festini, S. Molica, G. Lambertenghi Deliliers, F. Morabito, M. Ferrarini, A. Neri. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 94:suppl. 2(2009), pp. 135-135. ((Intervento presentato al 14. convegno Congress of the European hematology association tenutosi a Berlino nel 2009 [10.3324/haematol.13151].

Genome-wide DNA copy number analysis by SNP arrays of B-cell chronic lymphocytic leukemia reveals the presence of novel molecular lesions

L. Agnelli
Secondo
;
S. Fabris;M. Lionetti;K. Todoerti;G. Lambertenghi Deliliers;A. Neri
Ultimo
2009

Abstract

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 51Cr 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.
Dasatinib; Large granular lymphocyte; Lymphocytosis; Natural killer cells
Settore MED/15 - Malattie del Sangue
2009
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/65290
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