Evidence map›Paper›PMID 27127301›Full record

Trial reportBlood2016

Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.

Nakhle S Saba, Delong Liu, Sarah E M Herman, Chingiz Underbayev, Xin Tian, David Behrend, Marc A Weniger, Martin Skarzynski, Jennifer Gyamfi, Lorena Fontan and 9 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03529955 (A Phase 2, Open Label Single Arm Study for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis), which is not on this map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
11.9field-weighted citation impact, top 1% 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.

NCT03529955 phase2completednot on this mapstarted 2018, after this paper: background citation

A Phase 2, Open Label Single Arm Study for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis

TypeinterventionalSponsorTulane UniversityRan2018 to 2021Enrolled8ConditionsDermatomyositis, Adult TypeArmsApremilast 30mg
3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 162 citations in OpenAlex.

  1. Trial
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  5. Article
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  9. Review
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  11. The Novel Immunocompetent Eµ-SOX11CCND1 Mouse Model Phenotypically and Molecularly Resembles Human Mantle Cell Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  12. Goodbye flat lymphoma biology.FEBS letters · 2025
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Epstein-Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Article
  20. TRAF3 loss-of-function reveals the noncanonical NF-κB pathway as a therapeutic target in diffuse large B cell lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

36 more citing papers are in PubMed but not listed here.

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

19 authors at 4 institutions in 2 countries.

Nakhle S SabaHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Section of Hematology and Medical Oncology, Department of Medicine, Tulane University, New Orleans, LA;
Delong LiuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Sarah E M HermanHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Chingiz UnderbayevHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Xin TianOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
David BehrendHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Marc A WenigerHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Martin SkarzynskiHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Jennifer GyamfiHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Lorena FontanDivision of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY;
Ari MelnickDivision of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY;ORCID 0000-0002-8074-2287
Cliona GrantLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
Mark RoschewskiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
Alba NavarroInstitut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain; and.
Sílvia BeàInstitut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain; and.
Stefania PittalugaLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Kieron DunleavyLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
Wyndham H WilsonLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
Adrian WiestnerHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
National Institutes of Health · USConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESCornell University · USTulane University · 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
Novel therapies for Mantle Cell Lymphoma: targets, mechanisms, and prognosisZIAHL005076 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI WIESTNER, ADRIAN U · 2009 to 2019
$3.2M
MALT1 Targeted Therapy for B-Cell LymphomaR01CA187492 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MELNICK, ARI M. · 2014 to 2017
$1.4M
NCI NIH HHS R01 CA187492
6 · The paper itself

Abstract

To interrogate signaling pathways activated in mantle cell lymphoma (MCL) in vivo, we contrasted gene expression profiles of 55 tumor samples isolated from blood and lymph nodes from 43 previously untreated patients with active disease. In addition to lymph nodes, MCL often involves blood, bone marrow, and spleen and is incurable for most patients. Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL. However, the role of specific signaling pathways in the lymphomagenesis of MCL and the biologic basis for ibrutinib sensitivity of these tumors are unknown. Here, we demonstrate activation of B-cell receptor (BCR) and canonical NF-κB signaling specifically in MCL cells in the lymph node. Quantification of BCR signaling strength, reflected in the expression of BCR regulated genes, identified a subset of patients with inferior survival after cytotoxic therapy. Tumor proliferation was highest in the lymph node and correlated with the degree of BCR activation. A subset of leukemic tumors showed active BCR and NF-κB signaling apparently independent of microenvironmental support. In one of these samples, we identified a novel somatic mutation in RELA (E39Q). This sample was resistant to ibrutinib-mediated inhibition of NF-κB and apoptosis. In addition, we identified germ line variants in genes encoding regulators of the BCR and NF-κB pathway previously implicated in lymphomagenesis. In conclusion, BCR signaling, activated in the lymph node microenvironment in vivo, appears to promote tumor proliferation and survival and may explain the sensitivity of this lymphoma to BTK inhibitors.

Indexed as

ApoptosisLymphoma, Mantle-CellMutation, MissenseSignal TransductionTranscription Factor RelAAdenineAmino Acid SubstitutionDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansMalePiperidinesPyrazolesPyrimidinesReceptors, Antigen, B-CellAdenineibrutinibPiperidinesPyrazolesPyrimidinesReceptors, Antigen, B-CellRELA protein, humanTranscription Factor RelA

Identifiers

PMID27127301
PMCPMC4937360
OpenAlexW2345102372

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.