Evidence map›Paper›PMID 39255961›Full record

ArticleInternational journal of laboratory hematology2025

A new digital droplet PCR method for looking at epigenetics in diffuse large B-cell lymphomas: The role of BMI1, EZH2, and USP22 genes.

Alessio Lusci Gemignani, Robel Papotti, Riccardo Bomben, Valter Gattei, Samantha Pozzi, Valentina Donati, Stefania Bettelli, Elisa Forti, Giovanna Mansueto, Arianna Di Napoli and 10 more

Abstract read
In one paragraph

Article in International journal of laboratory hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
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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

20 authors.

Alessio Lusci GemignaniDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Robel PapottiInternational PhD School in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Riccardo BombenClinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Valter GatteiClinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Samantha PozziDipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.
Valentina DonatiPathology II, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Stefania BettelliPatologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.
Elisa FortiPatologia Molecolare e Medicina Predittiva, AOU Modena, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.
Giovanna MansuetoIRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
Arianna Di NapoliDepartment of Clinical and Molecular Medicine, Sapienza University, Sant'Andrea University Hospital, Rome, Italy.
Maria Christina CoxHaematology Department, King's College Hospital NHS Trust and UOC Ematologia, AOU Sant'Andrea, Roma, Italy.
Leonardo FlenghiDepartment of Emergency and Organ Transplantation, Azienda Ospedaliera di Perugia, Italy.
Pietro RossiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Guido VolpeDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Dimitri DardanisDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Clara BonoDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Francesca GuerriniDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Riccardo MorgantiSOD supporto statistico agli studi clinici, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Stefano SacchiDipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy.
Sara GalimbertiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID https://orcid.org/0000-0002-4620-0038

Funding

Rock & Peace foundation
6 · The paper itself

Abstract

introductionEpigenetics has been shown to be relevant in oncology: BMI1 overexpression has been reported in leukemias, EZH2 mutations have been found in follicular lymphoma, and USP22 seems to stabilize BMI1 protein. In this study, we measured the expression of BMI1, EZH2, and USP22 in lymph nodes from 56 diffuse large B-cell lymphoma (DLBCL) patients.

methodsA new multiplex digital droplet PCR (ddPCR) has been set up to measure the expression of 4 genes (BMI1, EZH2, USP22, and GAPDH) in the same reaction on RNA extracted from paraffin-embedded tissues.

resultsThe specificity of ddPCR was confirmed by a 100% alignment on the BLAST platform and its repeatability demonstrated by duplicates. A strict correlation between expression of BMI1 and EZH2 and BMI1 and USP22 has been found, and high expression of these genes was correlated with extra-nodal lymphomas. Progression-free survival (PFS) and overall survival (OS) were conditioned by IPI, bone marrow infiltration, and the complete response achievement. High levels of BMI1 and USP22 did not condition the response to therapy, but impaired the PFS, especially for patients defined at "high risk" based on the cell of origin (no germinal center [GCB]), high BCL2 expression, and IPI 3-5. In this subgroup, the probability of relapse/progression was twice higher than that of patients carrying low BMI1 and USP22 levels.

conclusionHigh expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.

Indexed as

Enhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticLymphoma, Large B-Cell, DiffusePolycomb Repressive Complex 1Polymerase Chain ReactionUbiquitin ThiolesteraseAdultAgedFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedBMI1 protein, humanEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanPolycomb Repressive Complex 1Ubiquitin ThiolesteraseUsp22 protein, humanBMI1ddPCRDLBCLEZH2USP22

Identifiers

PMID39255961
PMCPMC11725558

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