Evidence map›Paper›PMID 33327558›Full record

ArticleCancers2020

A Novel Platform to Test In Vivo Single Gene Dependencies in t(8,21) and t(15,17) AML Confirms Zeb2 as Leukemia Target.

Giulia De Conti, Alicja M Gruszka, Debora Valli, Andrea Umberto Cammarata, Matteo Righi, Massimiliano Mazza, Pier Giuseppe Pelicci

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

7 authors at 3 institutions in 1 country.

Giulia De ContiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.ORCID 0000-0002-2647-228X
Alicja M GruszkaDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.ORCID 0000-0002-5359-0281
Debora ValliDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.
Andrea Umberto CammarataDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.
Matteo RighiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.
Massimiliano MazzaImmunotherapy, Cell Therapy and Biobank, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l, 47014 Meldola, Italy.ORCID 0000-0001-9053-5743
Pier Giuseppe PelicciDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.
European Institute of Oncology · ITIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori · ITUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The increased usage of high-throughput technologies in cancer research, including genetic and drug screens, generates large sets of candidate targets that need to be functionally validated for their roles in tumor development. Thus, reliable and robust in vivo model systems are needed to perform reverse genetic experiments. Ideally, these models should allow for a conditional silencing of the target and an unambiguous identification of engineered cancer cells. Here, we present a platform consisting of: (i) t(8;21) and t(15;17) driven acute myeloid leukemia (AML) transgenic mice with constitutive expression of green fluorescent protein (GFP) and inducible expression of Cre recombinase, and (ii) REX, a modified pSico lentiviral vector for inducible shRNA expression and red fluorescent protein (RFP) as a selection marker. In this system, leukemic cells from transgenic mice are transduced with REX, flow sorted, and transplanted into syngeneic hosts. Gene interference is induced in established tumors by tamoxifen treatment. Dual-color cell fluorescence guides the in vivo identification of shRNA interfered AML cells, monitoring engraftment and disease progression. We tested the platform by inducing knockdown of Zeb2, a gene upregulated by AML1-ETO and PML-RARα oncogenes in pre-leukemic hematopoietic stem cell compartment, and observed a significant delay in leukemia onset. This proves the power and utility of the platform and confirms Zeb2 contribution to the pathogenesis of AML.

Indexed as

AMLAML1-ETOcandidate genesmouse modelPML-RAR

Identifiers

PMID33327558
PMCPMC7765008
OpenAlexW3113250015

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.