Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30149317
DOI
10.1016/j.leukres.2018.08.006
PII: S0145-2126(18)30184-X
Knihovny.cz E-resources
- Keywords
- CLL cells, Chronic lymphocytic leukemia, HLA-DR, Ibrutinib, T cells,
- MeSH
- Adenine analogs & derivatives MeSH
- Time Factors MeSH
- CD4-Positive T-Lymphocytes metabolism pathology MeSH
- CD8-Positive T-Lymphocytes metabolism pathology MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * drug therapy metabolism pathology MeSH
- HLA-DR Antigens biosynthesis MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Proteins biosynthesis MeSH
- Piperidines MeSH
- Pyrazoles administration & dosage MeSH
- Pyrimidines administration & dosage MeSH
- Gene Expression Regulation, Leukemic drug effects MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenine MeSH
- HLA-DR Antigens MeSH
- ibrutinib MeSH Browser
- Neoplasm Proteins MeSH
- Piperidines MeSH
- Pyrazoles MeSH
- Pyrimidines MeSH
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 < 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.
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