Evidence map›Paper›PMID 29472719›Full record

ArticleLeukemia2018

Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

Matteo Zampini, Claudia Tregnago, Valeria Bisio, Luca Simula, Giulia Borella, Elena Manara, Carlo Zanon, Francesca Zonta, Valentina Serafin, Benedetta Accordi and 6 more

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Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 22 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

16 authors at 5 institutions in 1 country.

Matteo ZampiniIstituto di Ricerca Pediatrica (IRP)-Fondazione Città della Speranza, Haematology-Oncology Lab, Padova, Italy.
Claudia TregnagoWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Valeria BisioWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Luca SimulaDepartment of Biology, University of Rome Tor Vergata, Rome, Italy.
Giulia BorellaWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Elena ManaraIstituto di Ricerca Pediatrica (IRP)-Fondazione Città della Speranza, Haematology-Oncology Lab, Padova, Italy.ORCID http://orcid.org/0000-0002-1176-3359
Carlo ZanonIstituto di Ricerca Pediatrica (IRP)-Fondazione Città della Speranza, Haematology-Oncology Lab, Padova, Italy.
Francesca ZontaWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Valentina SerafinWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Benedetta AccordiWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Silvia CampelloDepartment of Biology, University of Rome Tor Vergata, Rome, Italy.
Barbara BuldiniWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Andrea PessionDepartment of Pediatrics, Sant'Orsola Hospital, University of Bologna, Bologna, Italy.
Franco LocatelliDepartment of Pediatric Onco-Haematology, IRCCS Bambino Gesù Children's Hospital, University of Pavia, Rome, Italy.
Giuseppe BassoWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy.
Martina PigazziWomen and Child Health Department, Haematology-Oncology Clinic and Lab, University of Padova, Padova, Italy. martina.pigazzi@unipd.it.
University of Padua · ITCittà della Speranza Foundation · ITUniversity of Rome Tor Vergata · ITUniversity of Bologna · ITUniversity of Pavia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

Indexed as

EpigenomicsGenetic HeterogeneityTranslocation, GeneticAdolescentBlast CrisisCell AdhesionCell MovementChildChild, PreschoolChromosomes, Human, Pair 21Chromosomes, Human, Pair 8Core Binding Factor Alpha 2 SubunitCytoskeletonHumansLeukemia, Myeloid, AcuteRecurrenceCore Binding Factor Alpha 2 SubunitrhoB GTP-Binding ProteinRUNX1 protein, humanRUNX1T1 protein, humanRUNX1 Translocation Partner 1 Protein

Identifiers

PMID29472719
OpenAlexW2789822695

What OpenQuestion holds

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Registered trials

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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.