Evidence map›Paper›PMID 26089373›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo.

Sarah E M Herman, Rashida Z Mustafa, Jade Jones, Deanna H Wong, Mohammed Farooqui, Adrian Wiestner

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing 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

77 citing papers in PubMed, 106 citations in OpenAlex.

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  3. Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Sarah E M HermanHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Rashida Z MustafaHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Jade JonesHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland. Medical Research Scholars Program, NIH, Bethesda, Maryland.
Deanna H WongHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Mohammed FarooquiHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.
Adrian WiestnerHematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland. wiestnea@nhlbi.nih.gov.
National Heart Lung and Blood Institute · US

Funding

Tumor microenvironment in CLL and MCL: pathogenesis, targets, and therapyZIAHL002346 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI WIESTNER, ADRIAN U · 2009 to 2025
$29.8M
Howard Hughes Medical InstituteIntramural NIH HHS ZIA HL002346
6 · The paper itself

Abstract

purposeIbrutinib leads to a transient lymphocytosis in patients with chronic lymphocytic leukemia (CLL) that develops within hours of starting drug and is due to the efflux of cells from lymphoid tissues into the blood. We therefore sought to investigate the in vivo effect of ibrutinib on migration and adhesion of CLL cells. EXPERIMENTAL

designPatients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays.

resultsAdhesion of CLL cells to fibronectin was rapidly (within hours) and almost completely inhibited (median reduction 98% on day 28, P < 0.001), while the effect on migration to chemokines was more moderate (median reduction 64%, P = 0.008) and less uniform. Although cell surface expression of key adhesion molecules such as CD49d, CD29, and CD44 were modestly reduced, this was only apparent after weeks of treatment. Stimulation of CLL cells from patients on ibrutinib with PMA, which activates PKC independent of BTK, restored the ability of the cells to adhere to fibronectin in a VLA-4-dependent manner. Finally, the addition of ibrutinib to CLL cells adhered to fibronectin in vitro caused the detachment of 17% of the cells, on average; consisten t with in vivo observations of an increasing lymphocytosis within 4 hours of starting ibrutinib.

conclusionsInhibition of BTK and VLA-4-dependent adhesion of CLL cells to stroma and stromal components provides a mechanistic explanation for the treatment-induced lymphocytosis and may reduce CD49d-dependent prosurvival signals in the tissue microenvironment.

Indexed as

AdenineAgammaglobulinaemia Tyrosine KinaseAgedCell AdhesionFemaleFibronectinsHumansIntegrin alpha4beta1Leukemia, Lymphocytic, Chronic, B-CellLymphocytosisMalePiperidinesProtein Kinase CProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesAdenineAgammaglobulinaemia Tyrosine KinaseBTK protein, humanFibronectinsibrutinibIntegrin alpha4beta1PiperidinesProtein Kinase CProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidines

Identifiers

PMID26089373
PMCPMC4609275
OpenAlexW2154360891

What OpenQuestion holds

Textmetadata
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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.