Evidence map›Paper›PMID 27480113›Full record

ArticleBlood2016

Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis.

Gabriela Pavlasova, Marek Borsky, Vaclav Seda, Katerina Cerna, Jitka Osickova, Michael Doubek, Jiri Mayer, Raffaele Calogero, Martin Trbusek, Sarka Pospisilova and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 107 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 3 countries.

Gabriela PavlasovaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Marek BorskyDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Vaclav SedaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Katerina CernaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Jitka OsickovaDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Michael DoubekDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Jiri MayerDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Raffaele CalogeroDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy;
Martin TrbusekDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Sarka PospisilovaDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Matthew S DavidsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; and.
Thomas J KippsMoores Cancer Center, Department of Medicine, University of California San Diego, La Jolla, CA.
Jennifer R BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; and.
Marek MrazCentral European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic;
Masaryk University · CZCentral European Institute of Technology – Masaryk University · CZUniversity Hospital Brno · CZDana-Farber Cancer Institute · USUniversity of California, San Diego · USUniversity of Turin · IT

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534
6 · The paper itself

Abstract

Agents targeting B-cell receptor (BCR) signaling-associated kinases such as Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase can induce mobilization of neoplastic B cells from the lymphoid tissues into the blood, which makes them potentially ideal to combine with anti-CD20 monoclonal antibodies (such as rituximab, obinutuzumab, or ofatumumab) for treatment of B-cell lymphomas and chronic lymphocytic leukemia (CLL). Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20 (MS4A1) expression in vivo. We observed that CLL cells that have recently exited the lymph node microenvironment and moved into the peripheral blood (CXCR4(dim)CD5(bright) subpopulation) have higher cell surface levels of CD20 than the cells circulating in the bloodstream for a longer time (CXCR4(bright)CD5(dim) cells). We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1α, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1α-mediated CD20 upregulation. Ibrutinib also downmodulated Mcl1 levels in CLL cells in vivo and in coculture with stromal cells. Overall, our study provides a first detailed mechanistic explanation of CD20 expression regulation in the context of chemokine signaling and microenvironmental interactions, which may have important implications for microenvironment-targeting therapies.

Indexed as

AdenineAntigens, CD20Chemokine CXCL12Gene Expression Regulation, NeoplasticHumansLeukemia, Lymphocytic, Chronic, B-CellPiperidinesPyrazolesPyrimidinesReceptors, CXCR4Signal TransductionTumor Cells, CulturedUp-RegulationAdenineAntigens, CD20Chemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanibrutinibPiperidinesPyrazolesPyrimidinesReceptors, CXCR4

Identifiers

PMID27480113
PMCPMC5291297
OpenAlexW2482579995

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.