Evidence map›Paper›PMID 39160538›Full record

ArticleJournal of hematology & oncology2024

Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients.

Adriane Halik, Marlon Tilgner, Patricia Silva, Natalia Estrada, Robert Altwasser, Ekaterina Jahn, Michael Heuser, Hsin-An Hou, Marta Pratcorona, Robert K Hills and 22 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

32 authors.

Adriane Halik *Department of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Marlon Tilgner *Department of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Patricia Silva *Department of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Natalia EstradaDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Robert AltwasserDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Ekaterina JahnDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Michael HeuserDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Hsin-An HouDivision of Hematology, Department of Internal Medicine, and Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei City, Taiwan.
Marta PratcoronaHospital de la Santa Creu i Sant Pau. Institut de Recerca Sant Pau. Department of Medicine, Universitat Autonoma of Barcelona, Barcelona, Spain.
Robert K HillsNuffield Department of Population Health, University of Oxford, Oxford, UK.
Klaus H MetzelerDepartment of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
Laurene FenwarthUnité Mixte de Recherche (UMR) 9020-UMR1277, Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, Centre National de la Recherche Scientifique (CNRS), INSERM, Centre Hospitalo-Universitaire (CHU) Lille, Institut de Recherche sur le Cancer de Lille (IRCL), Lille, France.
Anna DolnikDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Christine TerreLaboratoire de Cytogénétique, Service de Biologie, CH de Versailles, Le Chesnay, France.
Klara KoppDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Olga BlauDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Martin SzyskaDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Friederike ChristenDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Jan KrönkeDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Loïc VasseurHematology Department, Saint Louis Hospital, AP-HP, Paris, France.
Bob LöwenbergDepartment of Hematology, Erasmus MC Cancer Institute, and Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Jordi EsteveHematology Department, IDIBAPS, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
Peter J M ValkDepartment of Hematology, Erasmus MC Cancer Institute, and Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Matthieu DuchmannInstitut de Recherche Saint-Louis (IRSL), Institut National de la Santé et de la Recherche Médicale (INSERM) U944, Centre National de la Recherche Scientifique (CNRS) UMR 7212 GenCellDis, Université Paris Cité, Paris, France.
Wen-Chien ChouDivision of Hematology, Department of Internal Medicine, and Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei City, Taiwan.
David C LinchDepartment of Haematology, University College London Cancer Institute, London, UK.
Hartmut DöhnerDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Rosemary E GaleDepartment of Haematology, University College London Cancer Institute, London, UK.
Konstanze DöhnerDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Lars BullingerDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Kenichi YoshidaDivision of Cancer Evolution, National Cancer Center Research Institute, Tokyo, Japan.
Frederik DammDepartment of Hematology, Oncology, and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. frederik.damm@charite.de.

Funding

Bundesministerium für Bildung und Forschung MEET-AML 01KU2014Deutsche Forschungsgemeinschaft FOR 2674Deutsche Krebshilfe 70113643José Carreras Leukämie-Stiftung 03 R/2020National Cancer Center Research and Development Funds 2022-A-1
6 · The paper itself

Abstract

backgroundDeletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood.

methodsTo discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines.

resultsIn the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7-most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or -7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66-3.86]; P < 0.001; PTPN11: HR, 2.24 [95% CI 1.56-3.22]; P < 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25-4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33-4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30-0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26-0.96]; P = 0.036).

conclusionThis work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation.

Indexed as

Chromosomes, Human, Pair 7Leukemia, Myeloid, AcuteAdolescentAdultAgedAged, 80 and overChromosome AberrationsCohort StudiesDNA Copy Number VariationsExome SequencingFemaleGenomicsHumansMaleMiddle AgedMutationProtein Tyrosine Phosphatase, Non-Receptor Type 11TP53 protein, humanTumor Suppressor Protein p53AMLComplex karyotypedel(7q)IDH2KMT2CMonosomy 7PTPN11TP53

Identifiers

PMID39160538
PMCPMC11331663

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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.