Evidence map›Paper›PMID 38834613›Full record

ArticleNature communications2024

Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML.

Matteo Marchesini, Andrea Gherli, Elisa Simoncini, Lucas Moron Dalla Tor, Anna Montanaro, Natthakan Thongon, Federica Vento, Chiara Liverani, Elisa Cerretani, Anna D'Antuono and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

34 authors.

Matteo MarchesiniDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Andrea Gherli *Department of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0003-3643-0056
Elisa Simoncini *Department of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0002-7488-8642
Lucas Moron Dalla Tor *Department of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0002-6080-7864
Anna MontanaroDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Natthakan ThongonDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Federica VentoTranslational Hematology and Chemogenomics Laboratory, University of Parma, Parma, Italy.
Chiara LiveraniIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Elisa CerretaniTranslational Hematology and Chemogenomics Laboratory, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0002-7622-5009
Anna D'AntuonoDepartment of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0002-2935-3286
Luca PagliaroDepartment of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0001-5500-3522
Raffaella ZamponiDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Chiara SpadazziIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Elena FolliniHematology and BMT Unit, Azienda USL Piacenza, Piacenza, Italy.
Benedetta CambòHematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Mariateresa GiaimoDepartment of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0002-8748-7012
Angela FalcoDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Gabriella SammarelliHematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Giannalisa TodaroHematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Sabrina BonominiHematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Valentina AdamiHigh-Throughput Screening Core Facility, CIBIO, University of Trento, Trento, Italy.
Silvano PiazzaHigh-Throughput Screening Core Facility, CIBIO, University of Trento, Trento, Italy.ORCID http://orcid.org/0000-0002-7156-5434
Claudia CorboUniversity of Milano-Bicocca, Department of Medicine and Surgery, NANOMIB Center, Monza, Italy.ORCID http://orcid.org/0000-0001-6468-2571
Bruno LorussoDepartment of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0003-1688-7841
Federica MezzasomaInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria Della Misericordia Hospital, Perugia, Italy.ORCID http://orcid.org/0000-0003-3158-3408
Costanza Anna Maria LagrastaDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Maria Paola MartelliInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria Della Misericordia Hospital, Perugia, Italy.ORCID http://orcid.org/0000-0001-9139-1729
Roberta La StarzaInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria Della Misericordia Hospital, Perugia, Italy.
Antonio CuneoDepartment of Medical Science, University of Ferrara, Ferrara, Italy.
Franco Aversa
Cristina MecucciInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria Della Misericordia Hospital, Perugia, Italy.ORCID http://orcid.org/0000-0002-1623-0148
Federico QuainiDepartment of Medicine and Surgery, University of Parma, Parma, Italy.ORCID http://orcid.org/0000-0003-2377-4810
Simona CollaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6583-8910
Giovanni RotiDepartment of Medicine and Surgery, University of Parma, Parma, Italy. giovanni.roti@unipr.it.ORCID http://orcid.org/0000-0002-8664-950X

Funding

Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 17107
6 · The paper itself

Abstract

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, here we dissect the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstitute the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 (PA2G4) protein. PA2G4 overexpression rescues AML cells from the inhibitory effects of HDACis, while genetic and small molecule inhibition of PA2G4 abrogates EVI1 in 3q26 AML cells, including in patient-derived leukemia xenografts. This study positions PA2G4 at the crosstalk of the EVI1 leukemogenic signal for developing new therapeutics and urges the use of HDACis-based combination therapies in patients with 3q26 AML.

Indexed as

Chromosomes, Human, Pair 3Histone Deacetylase InhibitorsLeukemia, Myeloid, AcuteMDS1 and EVI1 Complex Locus ProteinProteogenomicsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, LeukemicHumansMiceProto-Oncogene Proteins c-mycRNA-Binding ProteinsXenograft Model Antitumor AssaysAdaptor Proteins, Signal TransducingHistone Deacetylase InhibitorsMDS1 and EVI1 Complex Locus ProteinMECOM protein, humanMYC protein, humanPA2G4 protein, humanProto-Oncogene Proteins c-mycRNA-Binding Proteins

Identifiers

PMID38834613
PMCPMC11150407

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.