Evidence map›Paper›PMID 36480300›Full record

ArticleJCI insight2023

Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Friedrich Stölzel, Sarah E Fordham, Devi Nandana, Wei-Yu Lin, Helen Blair, Claire Elstob, Hayden L Bell, Brigitte Mohr, Leo Ruhnke, Desiree Kunadt and 34 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 9 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

44 authors at 11 institutions in 4 countries.

Friedrich StölzelMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Sarah E FordhamTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Devi NandanaTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Wei-Yu LinTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Helen BlairTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Claire ElstobTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Hayden L BellTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Brigitte MohrMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Leo RuhnkeMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Desiree KunadtMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Claudia DillMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Daniel AllsopTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Rachel PiddockTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Emmanouela-Niki SouraTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Catherine ParkTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Mohd FadlyTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Thahira RahmanTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Abrar AlharbiTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Manja WobusMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Heidi AltmannMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Christoph RölligMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Lisa WagenführMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
Gail L JonesDepartment of Hematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Tobias MenneDepartment of Hematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Graham H JacksonDepartment of Hematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Helen J MarrDepartment of Hematology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Jude FitzgibbonBarts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Kenan OnelIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Manja MeggendorferMLL Munich Leukemia Laboratory, Munich, Germany.
Amber RobinsonTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Zuzanna BziukTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Emily BowesTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Olaf HeidenreichTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Torsten HaferlachMLL Munich Leukemia Laboratory, Munich, Germany.
Sara VillarDepartment of Hematology, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Beñat AricetaHematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, Navarra, Spain.
Rosa Ayala DiazHematology Department, Hospital 12 de Octubre (i+12), Centro Nacional de Investigaciones Oncológicas (CNIO), Complutense University, Madrid, Spain.
Steven J AltschulerDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, California, USA.
Lani F WuDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, San Francisco, California, USA.
Felipe ProsperDepartment of Hematology, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Pau MontesinosHospital Universitario y Politécnico La Fe, Valencia, Spain.
Joaquin Martinez-LopezHematology Department, Hospital 12 de Octubre (i+12), Centro Nacional de Investigaciones Oncológicas (CNIO), Complutense University, Madrid, Spain.
Martin BornhäuserMedical Clinic and Polyclinic I, University Hospital Dresden, Technical University of Dresden, Dresden, Germany.
James M AllanTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Newcastle University · GBTechnische Universität Dresden · DEFreeman Hospital · GBNavarre Institute of Health Research · ESMunich Leukemia Laboratory (Germany) · DEResearch Institute Hospital 12 de Octubre · ESUniversity of California, San Francisco · USHospital Universitari i Politècnic La Fe · ESIcahn School of Medicine at Mount Sinai · USNational Center for Tumor Diseases · DEQueen Mary University of London · GB

Funding

Cancer Research UK 13044
6 · The paper itself

Abstract

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Indexed as

DioxygenasesLeukemia, Myeloid, AcuteAnimalsAzacitidineDNA-Binding ProteinsHumansKaplan-Meier EstimateMiceMutationAzacitidineDioxygenasesDNA-Binding ProteinsTET2 protein, humanTet2 protein, mouseCancerHematologyLeukemiasMolecular genetics

Identifiers

PMID36480300
PMCPMC9977313
OpenAlexW4310954682

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.