Evidence map›Paper›PMID 28412727›Full record

ArticleOncotarget2017

ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia.

Giuseppe Germano, Giulia Morello, Sanja Aveic, Marica Pinazza, Sonia Minuzzo, Chiara Frasson, Luca Persano, Paolo Bonvini, Giampietro Viola, Silvia Bresolin and 5 more

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

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

16 citing papers in PubMed, 24 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

15 authors at 3 institutions in 1 country.

Giuseppe GermanoFoundation Institute of Pediatric Research Città della Speranza, Padova, Italy.
Giulia MorelloFoundation Institute of Pediatric Research Città della Speranza, Padova, Italy.
Sanja AveicFoundation Institute of Pediatric Research Città della Speranza, Padova, Italy.
Marica PinazzaDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
Sonia MinuzzoDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
Chiara FrassonDepartment of Woman and Child Health, University of Padova, Italy.
Luca PersanoFoundation Institute of Pediatric Research Città della Speranza, Padova, Italy.
Paolo BonviniFoundation Institute of Pediatric Research Città della Speranza, Padova, Italy.
Giampietro ViolaDepartment of Woman and Child Health, University of Padova, Italy.
Silvia BresolinDepartment of Woman and Child Health, University of Padova, Italy.
Claudia TregnagoDepartment of Woman and Child Health, University of Padova, Italy.
Maddalena PaganinDepartment of Woman and Child Health, University of Padova, Italy.
Martina PigazziDepartment of Woman and Child Health, University of Padova, Italy.
Stefano IndraccoloImmunology and Molecular Oncology Unit, Istituto Oncologico Veneto IRCCS, Padova, Italy.
Giuseppe BassoDepartment of Woman and Child Health, University of Padova, Italy.
University of Padua · ITCittà della Speranza Foundation · ITIstituto Oncologico Veneto · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Zinc finger protein 521 (ZNF521) is a multiple zinc finger transcription factor and a strong candidate as regulator of hematopoietic stem cell homeostasis. Recently, independent gene expression profile studies have evidenced a positive correlation between ZNF521 mRNA overexpression and MLL-rearranged acute myeloid leukemia (AML), leaving open the question on the role of ZNF521 in this subtype of leukemia. In this study, we sought to analyze the effect of ZNF521 depletion on MLL-rearranged AML cell lines and MLL-AF9 xenograft primary cells. Knockdown of ZNF521 with short-hairpin RNA (shRNA) led to decreased leukemia proliferation, reduced colony formation and caused cell cycle arrest in MLL-rearranged AML cell lines. Importantly, we showed that loss of ZNF521 substantially caused differentiation of both MLL-rearranged cell lines and primary cells. Moreover, gene profile analysis in ZNF521-silenced THP-1 cells revealed a loss of MLL-AF9-directed leukemic signature and an increase of the differentiation program. Finally, we determined that both MLL-AF9 and MLL-ENL fusion proteins directly interacted with ZNF521 promoter activating its transcription. In conclusion, our findings identify ZNF521 as a critical effector of MLL fusion proteins in blocking myeloid differentiation and highlight ZNF521 as a potential therapeutic target for this subtype of leukemia.

Indexed as

Translocation, GeneticAdolescentAge FactorsAnimalsApoptosisCell Cycle CheckpointsCell DifferentiationCell Line, TumorCell ProliferationCell SurvivalChildChild, PreschoolDisease Models, AnimalDNA-Binding ProteinsGene Expression Regulation, LeukemicHeterograftsDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, Fusionzinc finger protein 521, humanacute myeloid leukemiamyeloid differentiationtranscriptionZNF521

Identifiers

PMID28412727
PMCPMC5432245
OpenAlexW2588369011

What OpenQuestion holds

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LicenceCC BY
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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.