Evidence map›Paper›PMID 24721775›Full record

ArticleLeukemia2014

Cytokine-driven loss of plasmacytoid dendritic cell function in chronic lymphocytic leukemia.

D Saulep-Easton, F B Vincent, M Le Page, A Wei, S B Ting, C M Croce, C Tam, F Mackay

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

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
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  17. Infection and cancer suppress pDC derived IFN-I.Current opinion in immunology · 2020
    Review
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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

8 authors at 4 institutions in 2 countries.

D Saulep-EastonDepartment of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
F B VincentDepartment of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
M Le PageDepartment of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
A Wei1] Department of Haematology, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, Australia [2] Australian Centre for Blood Diseases, Division of Blood Cancers, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
S B Ting1] Department of Haematology, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, Australia [2] Australian Centre for Blood Diseases, Division of Blood Cancers, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
C M CroceDepartment of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 460 West 12th Avenue, Columbus, OH, USA.
C TamDepartment of Haematology, Peter MacCallum Cancer Centre, St. Andrews's Place, East Melbourne, Victoria, Australia.
F MackayDepartment of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, Australia.
Monash University · AUPeter MacCallum Cancer Centre · AUThe Alfred Hospital · AUThe Ohio State University · US

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534Worldwide Cancer Research 14-0107
6 · The paper itself

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5(+)CD19(+) B cells in the peripheral blood, and in primary and secondary lymphoid organs. A major complication associated with CLL is severe recurrent infections, which are often fatal. Vulnerability to infection is due to a wide variety of immunological defects, yet the initiating events of immunodeficiency in CLL are unclear. Using CLL patient samples and a mouse model of CLL, we have discovered that plasmacytoid dendritic cells (pDCs), which underpin the activity of effector immune cells critical for anti-viral immunity and anti-tumor responses, are reduced in number and functionally impaired in progressive CLL. As a result, the levels of interferon alpha (IFNα) production, a cytokine critical for immunity, are markedly reduced. Lower pDC numbers with impaired IFNα production was due to the decreased expression of FMS-like tyrosine kinase 3 receptor (Flt3) and Toll-like receptor 9 (TLR9), respectively. Reduced Flt3 expression was reversed using inhibitors of TGF-β and TNF, an effect correlating with a reduction in tumor load. Defects in pDC numbers and function offer new insight into mechanisms underpinning the profound immunodeficiency affecting CLL patients and provide a potentially novel avenue for restoring immunocompetency in CLL.

Indexed as

Gene Expression Regulation, LeukemicAnimalsAntineoplastic AgentsCpG IslandsCytokinesDendritic CellsDisease Progressionfms-Like Tyrosine Kinase 3HumansInterferon-alphaLeukemia, Lymphocytic, Chronic, B-CellLymphocytesMiceToll-Like Receptor 9Transforming Growth Factor betaAntineoplastic AgentsCytokinesFLT3 protein, humanfms-Like Tyrosine Kinase 3Interferon-alphaTLR9 protein, humanToll-Like Receptor 9Transforming Growth Factor beta

Identifiers

PMID24721775
PMCPMC4100939
OpenAlexW2044686909

What OpenQuestion holds

Textmetadata
LicenceTDM
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.