Evidence map›Paper›PMID 26611474›Full record

ArticleHaematologica2016

A novel xenograft model to study the role of TSLP-induced CRLF2 signals in normal and malignant human B lymphopoiesis.

Olivia L Francis, Terry-Ann M Milford, Shannalee R Martinez, Ineavely Baez, Jacqueline S Coats, Karina Mayagoitia, Katherine R Concepcion, Elizabeth Ginelli, Cornelia Beldiman, Abigail Benitez and 13 more

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

Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  4. Article
  5. Frontiers in cell and developmental biology · 2022
    Review
  6. Article
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  9. Article
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  16. Oncotarget · 2017
    Article
  17. Suppressors and activators of JAK-STAT signaling at diagnosis and relapse of acute lymphoblastic leukemia in Down syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 3 institutions in 2 countries.

Olivia L FrancisLoma Linda University, CA, USA.
Terry-Ann M MilfordLoma Linda University, CA, USA.
Shannalee R MartinezLoma Linda University, CA, USA.
Ineavely BaezLoma Linda University, CA, USA.
Jacqueline S CoatsLoma Linda University, CA, USA.
Karina MayagoitiaLoma Linda University, CA, USA.
Katherine R ConcepcionLoma Linda University, CA, USA.
Elizabeth GinelliLoma Linda University, CA, USA.
Cornelia BeldimanLoma Linda University, CA, USA.
Abigail BenitezLoma Linda University, CA, USA.
Abby J WeldonLoma Linda University, CA, USA.
Keshav ArogyaswamyLoma Linda University, CA, USA.
Parveen ShirazLoma Linda University, CA, USA.
Ross FisherLoma Linda University, CA, USA.
Christopher L MorrisLoma Linda University, CA, USA.
Xiao-Bing ZhangLoma Linda University, CA, USA.
Valeri FilippovLoma Linda University, CA, USA.
Ben Van HandelNovogenix Laboratories, LLC, 1425 San Pablo, CA, USA.
Zheng GeThe First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Department of Hematology, Nanjing 210029, China Pennsylvania State University Medical College, Department of Pediatrics, Hershey, PA, USA.
Chunhua SongPennsylvania State University Medical College, Department of Pediatrics, Hershey, PA, USA.
Sinisa DovatPennsylvania State University Medical College, Department of Pediatrics, Hershey, PA, USA.
Ruijun Jeanna SuLoma Linda University, CA, USA.
Kimberly J PayneLoma Linda University, CA, USA kpayne@llu.edu.
Loma Linda University · USPennsylvania State University · USPenn State Milton S. Hershey Medical Center · US

Funding

NIH-LLU Initiative for Maximizing Student DiversityR25GM060507 · NIGMS · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2001 to 2022
$11.3M
Research Training/Education CoreP20MD006988 · NIMHD · LOMA LINDA UNIVERSITY · PI CASIANO, CARLOS A. · 2012 to 2016
$6.2M
The Role of Zinc Finger Genes in LeukemogenesisR01HL095120 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI DOVAT, SINISA · 2009 to 2013
$1.8M
Xenograft Model to Study Impact of CRLF2-Ligand in Hispanic Childhood B-ALLR21CA162259 · NCI · LOMA LINDA UNIVERSITY · PI PAYNE, KIMBERLY J · 2012 to 2013
$346k
NCI NIH HHS R21 CA162259NCI NIH HHS R21CA162259NHLBI NIH HHS R01 HL095120NIGMS NIH HHS 2R25 GM060507NIGMS NIH HHS R25 GM060507NIMHD NIH HHS P20 MD006988
6 · The paper itself

Abstract

Thymic stromal lymphopoietin (TSLP) stimulates in-vitro proliferation of human fetal B-cell precursors. However, its in-vivo role during normal human B lymphopoiesis is unknown. Genetic alterations that cause overexpression of its receptor component, cytokine receptor-like factor 2 (CRLF2), lead to high-risk B-cell acute lymphoblastic leukemia implicating this signaling pathway in leukemogenesis. We show that mouse thymic stromal lymphopoietin does not stimulate the downstream pathways (JAK/STAT5 and PI3K/AKT/mTOR) activated by the human cytokine in primary high-risk leukemia with overexpression of the receptor component. Thus, the utility of classic patient-derived xenografts for in-vivo studies of this pathway is limited. We engineered xenograft mice to produce human thymic stromal lymphopoietin (+T mice) by injection with stromal cells transduced to express the cytokine. Control (-T) mice were produced using stroma transduced with control vector. Normal levels of human thymic stromal lymphopoietin were achieved in sera of +T mice, but were undetectable in -T mice. Patient-derived xenografts generated from +T as compared to -T mice showed a 3-6-fold increase in normal human B-cell precursors that was maintained through later stages of B-cell development. Gene expression profiles in high-risk B-cell acute lymphoblastic leukemia expanded in +T mice indicate increased mTOR pathway activation and are more similar to the original patient sample than those from -T mice. +T/-T xenografts provide a novel pre-clinical model for understanding this pathway in B lymphopoiesis and identifying treatments for high-risk B-cell acute lymphoblastic leukemia with overexpression of cytokine-like factor receptor 2.

Indexed as

AnimalsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationHeterograftsHumansJanus Kinase 1Lymphocyte CountLymphopoiesisMiceMice, TransgenicPhosphatidylinositol 3-KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProto-Oncogene Proteins c-aktReceptors, CytokineCRLF2 protein, humanJak1 protein, mouseJanus Kinase 1mTOR protein, mousePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, CytokineRibosomal Protein S6 KinasesSTAT5 Transcription FactorTOR Serine-Threonine Kinases

Identifiers

PMID26611474
PMCPMC5004401
OpenAlexW2322605135

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.