Evidence map›Paper›PMID 36131042›Full record

ArticleLeukemia2022

A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome.

Héléna Boutzen, Seyed Ali Madani Tonekaboni, Michelle Chan-Seng-Yue, Alex Murison, Naoya Takayama, Nathan Mbong, Elvin Wagenblast, Elias Orouji, Andrea Arruda, Amanda Mitchell and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2022. 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
2.7field-weighted citation impact, top 8% 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, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Immune-epigenetic crosstalk in haematological malignancies.Frontiers in cell and developmental biology · 2023
    Review
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 2 countries.

Héléna BoutzenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Seyed Ali Madani TonekaboniDepartment of Medical Biophysics, University of Toronto, Toronto, ON, M5S 1A4, Canada.
Michelle Chan-Seng-YuePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.ORCID http://orcid.org/0000-0003-3773-9354
Alex MurisonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Naoya TakayamaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Nathan MbongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Elvin WagenblastPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.ORCID http://orcid.org/0000-0002-0709-2759
Elias OroujiPrincess Margaret Genomics Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Andrea ArrudaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Amanda MitchellPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Faiyaz NottaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Mathieu LupienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
Kerstin B KaufmannPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 0A3, Canada. john.dick@uhnresearch.ca.ORCID http://orcid.org/0000-0002-9527-8317
University Health Network · CAOntario Institute for Cancer Research · CAUniversity of Toronto · CA

Funding

CIHR RN380110–409786
6 · The paper itself

Abstract

Many cancers are organized as cellular hierarchies sustained by cancer stem cells (CSC), whose eradication is crucial for achieving long-term remission. Difficulties to isolate and undertake in vitro and in vivo experimental studies of rare CSC under conditions that preserve their original properties currently constitute a bottleneck for identifying molecular mechanisms involving coding and non-coding genomic regions that govern stemness. We focussed on acute myeloid leukemia (AML) as a paradigm of the CSC model and developed a patient-derived system termed OCI-AML22 that recapitulates the cellular hierarchy driven by leukemia stem cells (LSC). Through classical flow sorting and functional analyses, we established that a single phenotypic population is highly enriched for LSC. The LSC fraction can be easily isolated and serially expanded in culture or in xenografts while faithfully recapitulating functional, transcriptional and epigenetic features of primary LSCs. A novel non-coding regulatory element was identified with a new computational approach using functionally validated primary AML LSC fractions and its role in LSC stemness validated through efficient CRISPR editing using methods optimized for OCI-AML22 LSC. Collectively, OCI-AML22 constitutes a valuable resource to uncover mechanisms governing CSC driven malignancies.

Indexed as

Leukemia, Myeloid, AcuteNeoplastic Stem CellsHumans

Identifiers

PMID36131042
PMCPMC9613464
OpenAlexW4296690243

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.