Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30149317
DOI
10.1016/j.leukres.2018.08.006
PII: S0145-2126(18)30184-X
Knihovny.cz E-zdroje
- Klíčová slova
- CLL cells, Chronic lymphocytic leukemia, HLA-DR, Ibrutinib, T cells,
- MeSH
- adenin analogy a deriváty MeSH
- časové faktory MeSH
- CD4-pozitivní T-lymfocyty metabolismus patologie MeSH
- CD8-pozitivní T-lymfocyty metabolismus patologie MeSH
- chronická lymfatická leukemie * farmakoterapie metabolismus patologie MeSH
- HLA-DR antigeny biosyntéza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové proteiny biosyntéza MeSH
- piperidiny MeSH
- pyrazoly aplikace a dávkování MeSH
- pyrimidiny aplikace a dávkování MeSH
- regulace genové exprese u leukemie účinky léků MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenin MeSH
- HLA-DR antigeny MeSH
- ibrutinib MeSH Prohlížeč
- nádorové proteiny MeSH
- piperidiny MeSH
- pyrazoly MeSH
- pyrimidiny 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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