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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
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Haematol, S-17176 Stockholm, Sweden.
Karolinska Inst, Ctr Haematol & Regenerat Med, Stockholm, Sweden.
Karolinska Inst, Ctr Haematol & Regenerat Med, Stockholm, Sweden.
Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
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2018 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 183, no 2, p. 212-224Article in journal (Refereed) Published
Abstract [en]

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 CD19(+) 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.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 183, no 2, p. 212-224
Keywords [en]
chronic lymphocytic leukaemia, ibrutinib, chemokines, RNA sequencing, flow-cytometry
National Category
Hematology
Identifiers
URN: urn:nbn:se:uu:diva-387259DOI: 10.1111/bjh.15516ISI: 000449671500007PubMedID: 30125946OAI: oai:DiVA.org:uu-387259DiVA, id: diva2:1332132
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved

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Kamali-Moghaddam, MasoodShen, Qiujin

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