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dc.contributor.authorManukyan, Gayane
dc.contributor.authorTurcsányi, Peter
dc.contributor.authorMikulková, Zuzana
dc.contributor.authorGabčová, Gabriela
dc.contributor.authorUrbanová, Renata
dc.contributor.authorGajdoš, Petr
dc.contributor.authorŠmotková Kraiczová, Veronika
dc.contributor.authorZehnalová, Šárka
dc.contributor.authorPapajík, Tomáš
dc.contributor.authorKriegová, Eva
dc.identifier.citationLeukemia Research. 2018, vol. 72, p. 113-119.cs
dc.description.abstractThere is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib. We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL cells, T cells and monocytes. The immunophenotyping of CLL and immune cells in peripheral blood was performed on 16 high-risk CLL patients treated with ibrutinib. After early ibrutinib administration, the HLA-DR expression on CLL cells reduced (P = 0.032), accompanied by an increase in CLL cell counts in peripheral blood (P = 0.001). In vitro culturing of CLL cells with ibrutinib also revealed the reduction in the HLA-DR expression at protein and mRNA levels (P < 0.01). The decrease in HLA-DR on CLL cells after the first month was followed by the gradual increase of its expression by the 12th month (P = 0.001). A one-month follow-up resulted in elevated absolute counts of CD4(+) (P = 0.002) and CD8(+) (P < 0.001) T cells as well as CD4(+) and CD8(+) cells bearing HLA-DR (P < 0.01). The long-term administration of ibrutinib was associated with the increased numbers of CD4(+) bearing HLA-DR (P = 0.006) and elevation of HLA-DR expression on all monocyte subsets (P <= 0.004). Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells and monocytes. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.cs
dc.relation.ispartofseriesLeukemia Researchcs
dc.rights© 2018 Elsevier Ltd. All rights reserved.cs
dc.subjectchronic lymphocytic leukemiacs
dc.subjectCLL cellscs
dc.subjectT cellscs
dc.titleDynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemiacs
dc.description.sourceWeb of Sciencecs

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