Evidence map›Paper›PMID 25893290›Full record

ArticleOncogene2016

Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström macroglobulinemia.

B T Gaudette, B Dwivedi, K S Chitta, S Poulain, D Powell, P Vertino, X Leleu, S Lonial, A A Chanan-Khan, J Kowalski and 1 more

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

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. The Direction of Modern Therapies in Waldenström Macroglobulinaemia.Journal of cellular and molecular medicine · 2025
    Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Loss of TNFAIP3 enhances MYD88Blood cancer journal · 2018
    Article
  13. Article
  14. Review
  15. 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

11 authors at 4 institutions in 2 countries.

B T GaudetteDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
B DwivediWinship Cancer Institute, Emory University, Atlanta, GA, USA.
K S ChittaCancer Biology, Mayo Clinic, Jacksonville, FL, USA.
S PoulainService d'Hématologie Immunologie Cytogénétique, Hopital de Valenciennes, Valenciennes, France.
D PowellWinship Cancer Institute, Emory University, Atlanta, GA, USA.
P VertinoWinship Cancer Institute, Emory University, Atlanta, GA, USA.
X LeleuService des Maladies du Sang, Hopital Claude Huriez, CHRU Lille, Lille, France.
S LonialDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
A A Chanan-KhanHematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
J KowalskiWinship Cancer Institute, Emory University, Atlanta, GA, USA.
L H BoiseDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
Emory University · USMayo Clinic in Florida · USCentre Hospitalier de Valenciennes · FRHôpital Claude Huriez · FR

Funding

Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Arsenic-induced apoptosis in myelomaR01CA129968 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BOISE, LAWRENCE H. · 2009 to 2013
$1.8M
Proteosome inhibitor sensitivity in multiple myeloma: The role of ER stressR01CA127910 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BOISE, LAWRENCE H. · 2008 to 2012
$1.6M
NCI NIH HHS P30 CA138292NCI NIH HHS R01 CA127910NCI NIH HHS R01 CA129968
6 · The paper itself

Abstract

Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we examined Bcl-2 family expression in WM patients and cell lines. Unlike other B-lymphocyte-derived malignancies, which become dependent on expression of anti-apoptotic proteins to counter expression of pro-apoptotic proteins, WM samples expressed both pro- and anti-apoptotic Bcl-2 proteins at low levels similar to their normal B-cell and plasma cell counterparts. Three WM cell lines expressed pro-apoptotic Bcl-2 family members Bim or Bax and Bak at low levels, which determined their sensitivity to inducers of intrinsic apoptosis. In two cell lines, miR-155 upregulation, which is common in WM, was responsible for the inhibition of FOXO3a and Bim expression. Both antagonizing miR-155 to induce Bim and proteasome inhibition increased the sensitivity to ABT-737 in these lines indicating a lowering of the apoptotic threshold. In this manner, treatments that increase pro-apoptotic protein expression increase the efficacy of agents treated in combination in addition to direct killing.

Indexed as

ApoptosisApoptosis Regulatory Proteinsbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBcl-2-Like Protein 11Biphenyl CompoundsBortezomibCell Line, TumorForkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, NeoplasticHumansMembrane ProteinsMicroRNAsMultiple MyelomaNitrophenolsABT-737Apoptosis Regulatory ProteinsBAK1 protein, humanBAX protein, humanbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBCL2L11 protein, humanBcl-2-Like Protein 11Biphenyl CompoundsBortezomibForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanMembrane ProteinsMicroRNAsMIRN155 microRNA, humanNitrophenolsPiperazinesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Sulfonamides

Identifiers

PMID25893290
PMCPMC4874246
OpenAlexW2033823335

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.