Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes.

Palma M, Krstic A, Peña Perez L, Berglöf A, Meinke S, Wang Q, Blomberg KEM, Kamali-Moghaddam M, Shen Q, Jaremko G, Lundin J, De Paepe A, Höglund P, Kimby E, Österborg A, Månsson R, Smith CIE

Br. J. Haematol. 183 (2) 212-224 [2018-10-00; online 2018-08-20]

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.

Affinity Proteomics Uppsala [Collaborative]

PLA and Single Cell Proteomics [Collaborative]

PubMed 30125946

DOI 10.1111/bjh.15516

Crossref 10.1111/bjh.15516