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Ibrutinib induces r...
Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes
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- Palma, Marzia (author)
- Karolinska Institutet
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- Krstic, Aleksandra (author)
- Karolinska Institutet
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- Perez, Lucia Pena (author)
- Karolinska Institutet
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- Bergloef, Anna (author)
- Karolinska Institutet
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- Meinke, Stephan (author)
- Karolinska Institutet
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- Wang, Qing (author)
- Karolinska Institutet
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- Blomberg, K. Emelie M. (author)
- Karolinska Institutet
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- Kamali-Moghaddam, Masood (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Shen, Qiujin (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg
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- Jaremko, Georg (author)
- Karolinska Institutet
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- Lundin, Jeanette (author)
- Karolinska Institutet
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- De Paepe, Ayla (author)
- Karolinska Institutet
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- Hoeglund, Petter (author)
- Karolinska Institutet
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- Kimby, Eva (author)
- Karolinska Univ Hosp, Dept Haematol, S-17176 Stockholm, Sweden;Karolinska Inst, Ctr Haematol & Regenerat Med, Stockholm, Sweden
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- OEsterborg, Anders (author)
- Karolinska Institutet
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- Mansson, Robert (author)
- Karolinska Institutet
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- Smith, C. I. Edvard (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2018-08-20
- 2018
- English.
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In: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 183:2, s. 212-224
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- chronic lymphocytic leukaemia
- ibrutinib
- chemokines
- RNA sequencing
- flow-cytometry
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Palma, Marzia
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Krstic, Aleksand ...
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Perez, Lucia Pen ...
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Bergloef, Anna
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Meinke, Stephan
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Wang, Qing
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show more...
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Blomberg, K. Eme ...
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Kamali-Moghaddam ...
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Shen, Qiujin
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Jaremko, Georg
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Lundin, Jeanette
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De Paepe, Ayla
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Hoeglund, Petter
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Kimby, Eva
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OEsterborg, Ande ...
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Mansson, Robert
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Smith, C. I. Edv ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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British Journal ...
- By the university
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Uppsala University
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Karolinska Institutet