A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy
Tekijät: Mustjoki S, Auvinen K, Kreutzman A, Rousselot P, Hernesniemi S, Melo T, Lahesmaa-Korpinen AM, Hautaniemi S, Bouchet S, Molimard M, Smykla R, Lee FY, Vakkila J, Jalkanen S, Salmi M, Porkka K
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2013
Journal: Leukemia
Tietokannassa oleva lehden nimi: LEUKEMIA
Lehden akronyymi: LEUKEMIA
Numero sarjassa: 4
Vuosikerta: 27
Numero: 4
Aloitussivu: 914
Lopetussivu: 924
Sivujen määrä: 11
ISSN: 0887-6924
DOI: https://doi.org/10.1038/leu.2012.348
Tiivistelmä
Tyrosine kinase inhibitors (TKIs) have potent effects on malignant cells, and they also target kinases in normal cells, which may have therapeutic implications. Using a collection of 55 leukemia patients treated with TKI therapy (chronic myeloid leukemia, n = 47; acute lymphoblastic leukemia, n = 8), we found that dasatinib, a second-generation broad-spectrum TKI, induced a rapid, dose-dependent and substantial mobilization of non-leukemic lymphocytes and monocytes in blood peaking 1-2 h after an oral intake and the blood counts closely mirrored drug plasma concentration. A preferential mobilization was observed for natural killer (NK), NK T, B and gamma delta+ T cells. Mobilization was coupled with a more effective transmigration of leukocytes through an endothelial cell layer and improved cytotoxicity of NK cells. Platelet numbers decreased markedly after the drug intake in a proportion of patients. Similar effects on blood cell dynamics and function were not observed with any other TKI (imatinib, nilotinib and bosutinib). Thus, dasatinib induces a unique, rapid mobilization and activation of cytotoxic, extravasation-competent lymphocytes, which may not only enhance antileukemia immune responses but can also be causally related to the side-effect profile of the drug (pleural effusions, thrombocytopenia). Leukemia (2013) 27, 914-924; doi:10.1038/leu.2012.348
Tyrosine kinase inhibitors (TKIs) have potent effects on malignant cells, and they also target kinases in normal cells, which may have therapeutic implications. Using a collection of 55 leukemia patients treated with TKI therapy (chronic myeloid leukemia, n = 47; acute lymphoblastic leukemia, n = 8), we found that dasatinib, a second-generation broad-spectrum TKI, induced a rapid, dose-dependent and substantial mobilization of non-leukemic lymphocytes and monocytes in blood peaking 1-2 h after an oral intake and the blood counts closely mirrored drug plasma concentration. A preferential mobilization was observed for natural killer (NK), NK T, B and gamma delta+ T cells. Mobilization was coupled with a more effective transmigration of leukocytes through an endothelial cell layer and improved cytotoxicity of NK cells. Platelet numbers decreased markedly after the drug intake in a proportion of patients. Similar effects on blood cell dynamics and function were not observed with any other TKI (imatinib, nilotinib and bosutinib). Thus, dasatinib induces a unique, rapid mobilization and activation of cytotoxic, extravasation-competent lymphocytes, which may not only enhance antileukemia immune responses but can also be causally related to the side-effect profile of the drug (pleural effusions, thrombocytopenia). Leukemia (2013) 27, 914-924; doi:10.1038/leu.2012.348
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