Evidence map›Paper›PMID 34081901›Full record

ArticleMolecular cell2021

ATF3 coordinates serine and nucleotide metabolism to drive cell cycle progression in acute myeloid leukemia.

Daniela Di Marcantonio, Esteban Martinez, Joice S Kanefsky, Jacklyn M Huhn, Rashid Gabbasov, Anushk Gupta, John J Krais, Suraj Peri, YinFei Tan, Tomasz Skorski and 6 more

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
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  7. Review
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  9. mNature communications · 2025
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  12. Review
  13. International journal of biological sciences · 2025
    Article
  14. NAT10-mediated mRNA NNature cell biology · 2024
    Article
  15. Article
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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

16 authors at 5 institutions in 1 country.

Daniela Di MarcantonioBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Esteban MartinezBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Joice S KanefskyBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Jacklyn M HuhnBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Rashid GabbasovBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Anushk GuptaBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
John J KraisMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Suraj PeriMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
YinFei TanBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Tomasz SkorskiFels Cancer Institute for Personalized Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Adrienne DorranceDivision of Hematology/Oncology, Comprehensive Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Ramiro GarzonDivision of Hematology/Oncology, Comprehensive Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Aaron R GoldmanProteomics & Metabolomics Facility, Wistar Institute, Philadelphia, PA, USA.
Hsin-Yao TangProteomics & Metabolomics Facility, Wistar Institute, Philadelphia, PA, USA.
Neil JohnsonMolecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Stephen M SykesBlood Cell and Development Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; Division of Hematology/Oncology, Department of Pediatrics, Washington University of Saint Louis, Saint Louis, MO 63110, USA. Electronic address: s.m.sykes@wustl.edu.
Fox Chase Cancer Center · USThe Ohio State University Wexner Medical Center · USThe Wistar Institute · USTemple University · USWashington University in St. Louis · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Compensatory Mechanisms that Promote Homologous Recombination in BRCA1 Mutant CancersR01CA214799 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Neil Johnson · 2017 to 2026
$4.3M
AML mutation-guided drugging of DNA repairR01CA237286 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI MAZIN, ALEXANDER V, SKORSKI, TOMASZ · 2020 to 2024
$2.8M
PolQ as a novel therapeutic target in AMLR01CA244179 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI POMERANTZ, RICHARD T, SKORSKI, TOMASZ · 2020 to 2024
$2.7M
Advancing Cancer Research through Comprehensive Proteomics and Metabolomics AnalysesR50CA221838 · NCI · WISTAR INSTITUTE · PI Hsin-Yao Tang · 2017 to 2026
$2.1M
Targeting the Unfolded Protein Response in Leukemia Biology and Chemotherapy ResistanceR01CA227830 · NCI · WASHINGTON UNIVERSITY · PI SYKES, STEPHEN MATTHEW · 2019 to 2023
$1.9M
The role of microhomology-mediated end joining in Fanconi anemia pathogenesisR01HL150190 · NHLBI · RESEARCH INST OF FOX CHASE CAN CTR · PI JOHNSON, NEIL · 2020 to 2023
$1.9M
Purchase of a Q Exactive HF mass spectrometer system for metabolomicsS10OD023586 · OD · WISTAR INSTITUTE · PI SPEICHER, DAVID W. · 2017 to 2017
$600k
Defining and targeting the metabolic landscape in Acute Myeloid LeukemiaK99CA241370 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI DI MARCANTONIO, DANIELA · 2019 to 2020
$217k
NCI NIH HHS K99 CA241370NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA214799NCI NIH HHS R01 CA227830NCI NIH HHS R01 CA237286NCI NIH HHS R01 CA244179NCI NIH HHS R50 CA221838NHLBI NIH HHS R01 HL150190NIH HHS S10 OD023586
6 · The paper itself

Abstract

Metabolic reprogramming is a common feature of many human cancers, including acute myeloid leukemia (AML). However, the upstream regulators that promote AML metabolic reprogramming and the benefits conferred to leukemia cells by these metabolic changes remain largely unknown. We report that the transcription factor ATF3 coordinates serine and nucleotide metabolism to maintain cell cycling, survival, and the differentiation blockade in AML. Analysis of mouse and human AML models demonstrate that ATF3 directly activates the transcription of genes encoding key enzymatic regulators of serine synthesis, one-carbon metabolism, and de novo purine and pyrimidine synthesis. Total steady-state polar metabolite and heavy isotope tracing analyses show that ATF3 inhibition reduces de novo serine synthesis, impedes the incorporation of serine-derived carbons into newly synthesized purines, and disrupts pyrimidine metabolism. Importantly, exogenous nucleotide supplementation mitigates the anti-leukemia effects of ATF3 inhibition. Together, these findings reveal the dependence of AML on ATF3-regulated serine and nucleotide metabolism.

Indexed as

Cell CycleActivating Transcription Factor 3Cell Line, TumorHumansLeukemia, Myeloid, AcuteNeoplasm ProteinsNucleotidesSerineActivating Transcription Factor 3ATF3 protein, humanNeoplasm ProteinsNucleotidesSerineAMLATF3ATF4cell cycledifferentiationleukemiametabolismpurinespyrimidinesserine

Identifiers

PMID34081901
PMCPMC8452149
OpenAlexW3165884354

What OpenQuestion holds

Textmetadata
LicenceTDM
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.