Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia

•Ibrutinib influences the expression of HLA-DR on CLL cells.•Ibrutinib gradually increases HLA-DR levels on circulating monocyte subsets.•Immunomodulatory effect of ibrutinib on CLL, T cells, monocytes is time-dependent. There is the first evidence of changes in the kinetics of B cell antigen recept...

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Bibliographic Details
Published in:Leukemia research 2018-09, Vol.72, p.113-119
Main Authors: Manukyan, Gayane, Turcsanyi, Peter, Mikulkova, Zuzana, Gabcova, Gabriela, Urbanova, Renata, Gajdos, Petr, Smotkova Kraiczova, Veronika, Zehnalova, Sarka, Papajik, Tomas, Kriegova, Eva
Format: Article
Language:English
Subjects:
Aged
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
Chronic lymphocytic leukemia
CLL cells
Female
Gene Expression Regulation, Leukemic - drug effects
HLA-DR
HLA-DR Antigens - biosynthesis
Humans
Ibrutinib
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Male
Middle Aged
Neoplasm Proteins - biosynthesis
Pyrazoles - administration & dosage
Pyrimidines - administration & dosage
T cells
Time Factors
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Summary:•Ibrutinib influences the expression of HLA-DR on CLL cells.•Ibrutinib gradually increases HLA-DR levels on circulating monocyte subsets.•Immunomodulatory effect of ibrutinib on CLL, T cells, monocytes is time-dependent. There 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 
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2018.08.006