Evidence map›Paper›PMID 34244611›Full record

ArticleLeukemia2021

Single cell RNA sequencing of AML initiating cells reveals RNA-based evolution during disease progression.

L C Stetson, Dheepa Balasubramanian, Susan Pereira Ribeiro, Tammy Stefan, Kalpana Gupta, Xuan Xu, Slim Fourati, Anne Roe, Zachary Jackson, Robert Schauner and 12 more

Open access · greenAbstract read
In one paragraph

Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
10.1field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

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  15. Computational modeling of single-cell dynamics data.Briefings in bioinformatics · 2025
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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

22 authors at 5 institutions in 1 country.

L C Stetson *Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Dheepa Balasubramanian *Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Susan Pereira RibeiroDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Tammy StefanDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Kalpana GuptaDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Xuan XuDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Slim FouratiDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0001-6609-7587
Anne RoeDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Zachary JacksonDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0003-3655-8279
Robert SchaunerDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Ashish SharmaDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Banumathi TamilselvanDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Samuel LiDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Marcos de LimaCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-8568-4522
Tae Hyun HwangDepartment of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-6668-7269
Robert BalderasBD Biosciences, San Jose, CA, USA.
Yogen SaunthararajahCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-9757-1031
Jaroslaw MaciejewskiCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Thomas LaFramboiseCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Jill S Barnholtz-SloanCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
Rafick-Pierre SekalyDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA.
David N WaldDepartment of Pathology, Case Western Reserve University, Cleveland, OH, USA. dnw@case.edu.ORCID http://orcid.org/0000-0002-8695-1178
Case Western Reserve University · USCleveland Clinic · USBD Biosciences (United States) · USUniversity Hospitals Cleveland Medical Center · USUniversity Hospitals of Cleveland · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
Computational Genomic Epidemiology of Cancer (CoGEC) Training ProgramT32CA094186 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Thomas Louis LaFramboise, Rong Xu · 2017 to 2026
$2.6M
Integrating Clues from the Somatic Genome in the Search for Rare Germline Cancer Susceptibility VariantsR21CA249138 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI LAFRAMBOISE, THOMAS LOUIS · 2020 to 2021
$414k
NCI NIH HHS P30 CA043703NCI NIH HHS R21 CA249138NCI NIH HHS T32 CA094186NIAID NIH HHS T32 AI089474
6 · The paper itself

Abstract

The prognosis of most patients with AML is poor due to frequent disease relapse. The cause of relapse is thought to be from the persistence of leukemia initiating cells (LIC's) following treatment. Here we assessed RNA based changes in LICs from matched patient diagnosis and relapse samples using single-cell RNA sequencing. Previous studies on AML progression have focused on genetic changes at the DNA mutation level mostly in bulk AML cells and demonstrated the existence of DNA clonal evolution. Here we identified in LICs that the phenomenon of RNA clonal evolution occurs during AML progression. Despite the presence of vast transcriptional heterogeneity at the single cell level, pathway analysis identified common signaling networks involving metabolism, apoptosis and chemokine signaling that evolved during AML progression and become a signature of relapse samples. A subset of this gene signature was validated at the protein level in LICs by flow cytometry from an independent AML cohort and functional studies were performed to demonstrate co-targeting BCL2 and CXCR4 signaling may help overcome therapeutic challenges with AML heterogeneity. It is hoped this work will facilitate a greater understanding of AML relapse leading to improved prognostic biomarkers and therapeutic strategies to target LIC's.

Indexed as

AgedClonal EvolutionDisease ProgressionExome SequencingFemaleHumansInfantLeukemia, Myeloid, AcuteMaleMiddle AgedMutationPrognosisRecurrenceRNASequence Analysis, RNASignal TransductionRNA

Identifiers

PMID34244611
PMCPMC8807029
OpenAlexW3178135509

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.