Evidence map›Paper›PMID 27127886›Full record

ArticleOncotarget2016

Protein kinase D-dependent CXCR4 down-regulation upon BCR triggering is linked to lymphadenopathy in chronic lymphocytic leukaemia.

Stéphane Saint-Georges, Maude Quettier, Marouane Bouyaba, Stéphanie Le Coquil, Vanessa Laurienté, Lionel Guittat, Vincent Lévy, Florence Ajchenbaum-Cymbalista, Nadine Varin-Blank, Christine Le Roy and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

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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

11 authors at 6 institutions in 1 country.

Stéphane Saint-GeorgesINSERM U978, Bobigny, France.
Maude QuettierINSERM U978, Bobigny, France.
Marouane BouyabaAssistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Unité de Recherche Clinique, Bobigny, France.
Stéphanie Le CoquilINSERM U978, Bobigny, France.
Vanessa LaurientéINSERM U978, Bobigny, France.
Lionel GuittatINSERM U978, Bobigny, France.
Vincent LévyAssistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Unité de Recherche Clinique, Bobigny, France.
Florence Ajchenbaum-CymbalistaINSERM U978, Bobigny, France.
Nadine Varin-BlankINSERM U978, Bobigny, France.
Christine Le RoyINSERM U978, Bobigny, France.
Dominique LedouxINSERM U978, Bobigny, France.
Inserm · FRSorbonne Paris Cité · FREquipe de Recherche en Epidémiologie Nutritionnelle · FRAssistance Publique – Hôpitaux de Paris · FRHôpital Avicenne · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In Chronic Lymphocytic Leukemia (CLL), infiltration of lymph nodes by leukemic cells is observed in patients with progressive disease and adverse outcome. We have previously demonstrated that B-cell receptor (BCR) engagement resulted in CXCR4 down-regulation in CLL cells, correlating with a shorter progression-free survival in patients. In this study, we show a simultaneous down-regulation of CXCR4, CXCR5 and CD62L upon BCR triggering. While concomitant CXCR4 and CXCR5 down-regulation involves PKDs, CD62L release relies on PKC activation. BCR engagement induces PI3K-δ-dependent phosphorylation of PKD2 and 3, which in turn phosphorylate CXCR4 Ser324/325. Moreover, upon BCR triggering, PKD phosphorylation levels correlate with the extent of membrane CXCR4 decrease. Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR-responsive cells in vitro. In terms of pathophysiology, BCR-dependent CXCR4 down-regulation is observed in leukemic cells from patients with enlarged lymph nodes, irrespective of their IGHV mutational status. Taken together, our results demonstrate that PKD-mediated CXCR4 internalization induced by BCR engagement in B-CLL is associated with lymph node enlargement and suggest PKD as a potential druggable target for CLL therapeutics.

Indexed as

B-LymphocytesDown-RegulationGene Expression Regulation, LeukemicHumansLeukemia, Lymphocytic, Chronic, B-CellLymphadenopathyPhosphorylationProtein Kinase CProto-Oncogene Proteins c-bcrReceptors, CXCR4Signal TransductionTumor Cells, CulturedBCR protein, humanCXCR4 protein, humanProtein Kinase Cprotein kinase DProto-Oncogene Proteins c-bcrReceptors, CXCR4B-cell receptorCLLCXCR4/CXCR5lymphadenopathyprotein kinase D

Identifiers

PMID27127886
PMCPMC5173040
OpenAlexW2344872457

What OpenQuestion holds

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LicenceCC BY
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.