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Ibrutinib induces rapid down‐regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia‐related genes in blood and lymph nodes
Author(s) -
Palma Marzia,
Krstic Aleksandra,
Peña Perez Lucia,
Berglöf Anna,
Meinke Stephan,
Wang Qing,
Blomberg K. Emelie M.,
KamaliMoghaddam Masood,
Shen Qiujin,
Jaremko Georg,
Lundin Jeanette,
De Paepe Ayla,
Höglund Petter,
Kimby Eva,
Österborg Anders,
Månsson Robert,
Smith C. I. Edvard
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15516
Subject(s) - ibrutinib , chronic lymphocytic leukemia , inflammation , bruton's tyrosine kinase , lymph , chemokine , cancer research , peripheral blood mononuclear cell , immunology , b cell , medicine , biology , receptor , tyrosine kinase , leukemia , pathology , antibody , biochemistry , in vitro
Summary In chronic lymphocytic leukaemia ( CLL ) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes ( LN ) to peripheral blood ( PB ). Here, we characterized in depth the dynamics of ibrutinib‐induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Changes in plasma inflammation‐related biomarkers, CLL cell RNA expression, B‐cell activation and migration markers expression, and PB mononuclear cell populations were assessed. A significant reduction of 10 plasma inflammation markers, the majority of which were chemokines and not CLL ‐derived, was observed within hours, and was paralleled by very early increase of CD 19 + circulating cells. At the RNA level, significant and continuous changes in transcription factors and signalling molecules linked to B‐cell receptor signalling and CLL biology was observed in both PB and LN CLL cells already after 2 days of treatment. In conclusion, ibrutinib seems to instantly shut off an ongoing inflammatory response and interfere with diverse sensitive pathways in the LN .