Evidence map›Paper›PMID 25303368›Full record

ArticleBlood cancer journal2014

Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma.

A Barreca, C Martinengo, L Annaratone, L Righi, A Chiappella, M Ladetto, A Demurtas, L Chiusa, A Stacchini, N Crosetto and 2 more

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

Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

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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

12 authors at 4 institutions in 3 countries.

A BarrecaDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
C Martinengo1] Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy [2] Center for Experimental Medicine and Clinical Studies (CERMS), University of Torino, Torino, Italy.
L AnnaratoneDepartment of Medical Sciences, University of Torino, Torino, Italy.
L RighiDepartment of Clinical and Biological Sciences, University of Torino, Torino, Italy.
A ChiappellaASO San Giovanni Battista Hospital, Turin, Italy.
M LadettoDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
A DemurtasASO San Giovanni Battista Hospital, Turin, Italy.
L ChiusaASO San Giovanni Battista Hospital, Turin, Italy.
A StacchiniASO San Giovanni Battista Hospital, Turin, Italy.
N Crosetto1] Departments of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA [3] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA [4] Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, The Netherlands [5] University Medical Center Utrecht, Utrecht, The Netherlands.
A van Oudenaarden1] Departments of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA [3] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA [4] Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, The Netherlands [5] University Medical Center Utrecht, Utrecht, The Netherlands.
R Chiarle1] Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy [2] Center for Experimental Medicine and Clinical Studies (CERMS), University of Torino, Torino, Italy [3] Department of Pathology, Children's Hospital, Boston, MA, USA [4] Harvard Medical School, Boston, MA, USA.
Azienda Ospedaliero Universitaria San Giovanni Battista · ITUniversity of Turin · ITRoyal Netherlands Academy of Arts and Sciences · NLBoston Children's Museum · US

Funding

TRANS-NETWORK PROJECTSU54CA143874 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHAKRABORTY, ARUP K. · 2009 to 2013
$15.1M
NCI NIH HHS U54 CA143874NCI NIH HHS U54CA143874Worldwide Cancer Research 12-0216
6 · The paper itself

Abstract

Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients.

Indexed as

Gene Expression Regulation, NeoplasticImmunoglobulin Heavy ChainsLymphoma, FollicularProto-Oncogene Proteins c-bcl-2Cell Line, TumorChromosomes, Human, Pair 14Chromosomes, Human, Pair 18FemaleHumansIn Situ Hybridization, FluorescenceMaleRNA, MessengerRNA, NeoplasmTranslocation, GeneticBCL2 protein, humanImmunoglobulin Heavy ChainsProto-Oncogene Proteins c-bcl-2RNA, MessengerRNA, Neoplasm

Identifiers

PMID25303368
PMCPMC4220646
OpenAlexW2109045464

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.