Evidence map›Paper›PMID 35793392›Full record

ArticleBlood advances2022

In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies.

Francois E Mercier, Jiantao Shi, David B Sykes, Toshihiko Oki, Maja Jankovic, Cheuk Him Man, Youmna S Kfoury, Elizabeth Miller, Shutao He, Alexander Zhu and 5 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 15 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 6 institutions in 4 countries.

Francois E MercierCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0001-5324-2167
Jiantao ShiCenter for Cancer Evolution and Department of Data Science, Dana-Farber Cancer Institute, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.ORCID 0000-0002-0039-8800
David B SykesCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0002-9788-0221
Toshihiko OkiCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0001-9083-3126
Maja JankovicDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada.ORCID 0000-0003-2147-3811
Cheuk Him ManLi Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.ORCID 0000-0001-9478-2194
Youmna S KfouryCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0003-2495-3378
Elizabeth MillerCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.
Shutao HeState Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Beijing, China.
Alexander ZhuCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0002-0153-9134
Radovan VasicCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.
John DoenchBroad Institute, Cambridge, MA.ORCID 0000-0002-3707-9889
Alexandre OrthweinGerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada; and.ORCID 0000-0002-7350-3413
Franziska MichorDepartment of Stem Cell and Regenerative Biology, Harvard University, Boston, MA.
David T ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0001-9821-7133
Harvard University · USBroad Institute · USMcGill University · CAChinese Academy of Sciences · CNDana-Farber Cancer Institute · USUniversity of Hong Kong · HK

Funding

Project 3: Single Cell Measures of Intratumor Diversity for Optimal Breast Cancer TherapyU54CA193461 · NCI · DANA-FARBER CANCER INST · PI HOLLAND, ERIC C., MICHOR, FRANZISKA · 2015 to 2020
$11.2M
NCI NIH HHS U54 CA193461
6 · The paper itself

Abstract

Genome-wide CRISPR screens have been extremely useful in identifying therapeutic targets in diverse cancers by defining genes that are essential for malignant growth. However, most CRISPR screens were performed in vitro and thus cannot identify genes that are essential for interactions with the microenvironment in vivo. Here, we report genome-wide CRISPR screens in 2 in vivo murine models of acute myeloid leukemia (AML) driven by the KMT2A/MLLT3 fusion or by the constitutive coexpression of Hoxa9 and Meis1. Secondary validation using a focused library identified 72 genes specifically essential for leukemic growth in vivo, including components of the major histocompatibility complex class I complex, Cd47, complement receptor Cr1l, and the β-4-galactosylation pathway. Importantly, several of these in vivo-specific hits have a prognostic effect or are inferred to be master regulators of protein activity in human AML cases. For instance, we identified Fermt3, a master regulator of integrin signaling, as having in vivo-specific dependency with high prognostic relevance. Overall, we show an experimental and computational pipeline for genome-wide functional screens in vivo in AML and provide a genome-wide resource of essential drivers of leukemic growth in vivo.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsLeukemia, Myeloid, AcuteAnimalsHumansMiceMyeloid Ecotropic Viral Integration Site 1 ProteinSignal TransductionTumor MicroenvironmentMyeloid Ecotropic Viral Integration Site 1 Protein

Identifiers

PMID35793392
PMCPMC9631646
OpenAlexW4283835454

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.