Evidence map›Paper›PMID 28722170›Full record

ArticleInternational journal of cancer2017

Activation of the B-cell receptor successively activates NF-κB and STAT3 in chronic lymphocytic leukemia cells.

Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. New insights into the Lck-NF-κB signaling pathway.Frontiers in cell and developmental biology · 2023
    Review
  7. Article
  8. The Pt(International journal of molecular sciences · 2022
    Article
  9. Shikonin Derivatives fromNutrients · 2021
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. The Antidiabetic and Antinephritic Activities ofOxidative medicine and cellular longevity · 2018
    Article
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

13 authors at 1 institution in 2 countries.

Uri RozovskiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
David M HarrisDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ping LiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Zhiming LiuDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Preetesh JainDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ivo VeleticDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Alessandra FerrajoliDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Jan BurgerDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Philip ThompsonDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Nitin JainDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
William WierdaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Michael J KeatingDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Zeev EstrovDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-1623-3613
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 min, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hr. Here, we show that this process takes longer because it requires transcriptional activity of NF-κB. Using an electromobility shift assay, we found that incubation with IgM antibodies for 4 or 18 hr, but not 15 min, increased NF-κB DNA-binding of CLL cells and increased binding was translated to increased transcriptional activity. Hence, 42% of the 83 NF-κB target genes were constitutively expressed in all CLL cells prior to any inducible stimuli. However, activation of the BCR increased the number of NF-κB target genes with detectable expression by 23%. Remarkably, prolonged incubation with anti-IgM antibodies induced a time-dependent transcription, production and secretion of IL-6 protein. The IgM-induced production of IL-6 prompted the phosphorylation of STAT3 on tyrosine residues. This effect was inhibited by the JAK1/2 inhibitor of the JAK/STAT3 pathway ruxolitinib. Taken together, these results suggest that in CLL cells, constitutive tonic activation of NF-κB can be further enhanced by the BCR and that the BCR-induced activation of the JAK/STAT3 pathway depends on the NF-κB induced production of IL-6.

Indexed as

HumansInterleukin-6Leukemia, Lymphocytic, Chronic, B-CellNF-kappa BPhosphorylationReceptors, Antigen, B-CellSignal TransductionSTAT3 Transcription FactorTumor Cells, CulturedIL6 protein, humanInterleukin-6NF-kappa BReceptors, Antigen, B-CellSTAT3 Transcription Factorchronic lymphocytic Leukemianuclear factor κBphosphorylationsignal transducer and activator of transcription 3

Identifiers

PMID28722170
PMCPMC5749978
OpenAlexW2737438197

What OpenQuestion holds

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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.