Evidence map›Paper›PMID 40961937›Full record

ArticleCell metabolism2025

OGFOD1 enables AML chemo- and nutrient stress resistance by regulating protein synthesis.

Christina Mayerhofer, Dan Li, Trine Kristiansen, Ernst Mayerhofer, Azeem Sharda, Giulia Schiroli, Karin Gustafsson, Lingli He, Michael Mazzola, Sam Keyes and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Hyperpolarization of [1-Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Dual relevance ofFrontiers in oncology · 2026
    Article
  4. 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

20 authors.

Christina MayerhoferCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Dan LiCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Trine KristiansenCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Ernst MayerhoferBroad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Azeem ShardaCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Giulia SchiroliCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Karin GustafssonCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Lingli HeCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Michael MazzolaCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Sam KeyesCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Anna KiemCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Eve CromptonCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Yanxin XuCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Sovannarith KormCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Zhixun DouCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Charles VidoudezHarvard Center for Mass Spectrometry, Harvard University, Cambridge, MA, USA.
Peter G MillerCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Nick van Gastelde Duve Institute, UCLouvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.
Timothy A GraubertHarvard Medical School, Boston, MA, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, USA.
David T ScaddenCenter for Regenerative Medicine and Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: david_scadden@harvard.edu.

Funding

Transcriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI David T Scadden · 2017 to 2026
$24.6M
Molecular, Cellular, & Developmental Dynamics PhD ProgramT32GM007226 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI VAN VACTOR, DAVID L. · 1985 to 2021
$14.4M
Targeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI GRAUBERT, TIMOTHY A · 2017 to 2021
$10.6M
Training in Pharmacological SciencesT32GM132089 · NIGMS · HARVARD MEDICAL SCHOOL · PI DAVID E. GOLAN, Timothy J Mitchison · 2019 to 2026
$3.7M
Cap-Dependency in Hematopoietic Stem and Progenitor Cell TranslationF31HL158020 · NHLBI · HARVARD MEDICAL SCHOOL · PI MAZZOLA, MICHAEL · 2021 to 2023
$81k
NCI NIH HHS P50 CA206963NHLBI NIH HHS F31 HL158020NHLBI NIH HHS P01 HL131477NIGMS NIH HHS T32 GM007226NIGMS NIH HHS T32 GM132089
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in chemoresistant cells in vivo before overt relapse, identifying altered branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDXs) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression with low BCAA catabolism. Restricting BCAAs further reduced chemoresistant AML cells, but relapse still occurred. Among the persisting cells, we found an unexpected increase in protein production. This was accompanied by elevated translation of 2-oxoglutarate- and iron-dependent oxygenase 1 (OGFOD1), a known ribosomal dioxygenase that adjusts the fidelity of tRNA anticodon pairing with coding mRNA. We found that OGFOD1 upregulates protein synthesis in AML, driving disease aggressiveness. Inhibiting OGFOD1 impaired translation processing, decreased protein synthesis and improved animal survival even with chemoresistant AML while sparing normal hematopoiesis. Leukemic cells can therefore persist despite the stress of chemotherapy and nutrient deprivation through adaptive control of translation. Targeting OGFOD1 may offer a distinctive, translation-modifying means of reducing the chemopersisting cells that drive relapse.

Indexed as

DioxygenasesDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteNutrientsProtein BiosynthesisStress, PhysiologicalAmino Acids, Branched-ChainAnimalsCell Line, TumorFemaleHumansMiceAmino Acids, Branched-ChainDioxygenasesNutrientsacute myeloid leukemiaBCAAchemoresistancemetabolismOGFOD1protein biosynthesisRibo-seqribosome pausingtranslation accuracy

Identifiers

PMID40961937
PMCPMC12490346

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.