ArticleNature communications2017
RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia.
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Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
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Who cites it
65 citing papers in PubMed, 138 citations in OpenAlex.
- Trial
- Azacitidine (VidazaPaediatric drugs · 2023Trial
- Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial.Blood advances · 2021Trial
- Genomic Characterization of RTK-RAS Pathway Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Medical sciences (Basel, Switzerland) · 2026Article
- Article
- Genomic Characterization of Epigenetic Regulator Gene Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Epigenomes · 2026Article
- Clinical Phenotype, Molecular Architecture, and Survival Follow-Up in NRAS- and KRAS-Mutated Juvenile Myelomonocytic Leukemia.Cancers · 2026Article
- Review
- Error-corrected next-generation sequencing for profiling the subclonal genetic architecture of juvenile myelomonocytic leukemia.Leukemia · 2026Article
- Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Clinical and molecular characterization of patients with juvenile myelomonocytic leukaemia.British journal of haematology · 2025Article
- Epigenetic risk stratification in juvenile myelomonocytic leukemia by targeted methylation analysis of the BMP4 locus.Clinical epigenetics · 2025Article
- Assessment of peripheral blood DNA methylation signatures as pharmacodynamic and predictive biomarkers during azacitidine therapy in juvenile myelomonocytic leukaemia: Results of the EWOG-MESRAT study.British journal of haematology · 2025Article
- Article
- Celebrating Ulrik Ringborg: Multi-Omics-Based Patient Stratification for Precision Cancer Treatment.Biomolecules · 2025Review
- Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.Stem cell research & therapy · 2024Article
- Phenotypic profiling of CD34Haematologica · 2024Article
- Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study.Frontiers in immunology · 2024Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 15 institutions in 11 countries.
Daniel B LipkaRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany. d.lipka@dkfz.de.ORCID http://orcid.org/0000-0001-5081-7869
Tania WitteRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4287-1608
Reka TothComputational Epigenomics Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Jing YangDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Manuel WiesenfarthDivision of Biostatistics, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Peter NöllkeDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0281-4732
Alexandra FischerDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.
David BrocksCancer Epigenetics Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Zuguang GuDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Jeongbin ParkDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Brigitte StrahmDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.
Marcin WlodarskiDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.ORCID http://orcid.org/0000-0001-6638-9643
Ayami YoshimiDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.
Rainer ClausDivision of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Hugstetter Strasse 55, 79106, Freiburg, Germany.
Michael LübbertDivision of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Hugstetter Strasse 55, 79106, Freiburg, Germany.
Hauke BuschInstitute of Molecular Medicine and Cell Research, University of Freiburg, Stefan-Meier-Strasse 17, 79104, Freiburg, Germany.
Melanie BoerriesInstitute of Molecular Medicine and Cell Research, University of Freiburg, Stefan-Meier-Strasse 17, 79104, Freiburg, Germany.
Mark HartmannRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4072-4658
Maximilian SchönungRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-9778-9698
Umut KilikRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Jens LangsteinRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Justyna A WierzbinskaRegulation of Cellular Differentiation Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5536-3501
Caroline PabstDepartment of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, INF 410, 69120, Heidelberg, Germany.
Swati GargDepartment of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, INF 410, 69120, Heidelberg, Germany.
Albert CataláDepartment of Hematology and Oncology, Hospital Sant Joan de Déu, Passeig de Sant Joan de Déu, 2, 08950, Esplugues de Llobrega, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0133-1752
Barbara De MoerlooseDepartment of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
Michael DworzakSt. Anna Children's Hospital and Children's Cancer Research Institute, Medical University of Vienna, Zimmermannplatz 10, 1090, Vienna, Austria.
Henrik HasleDepartment of Pediatrics, Aarhus University Hospital Skejby, Palle Juul-Jensens Boulevard 82, 8200, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-3976-9231
Franco LocatelliDepartment of Pediatric Hematology and Oncology, Bambino Gesú Children's Hospital, University of Pavia, Piazza S. Onofrio 4, Rome, 00165, Italy.
Riccardo MasettiDepartment of Pediatric Oncology and Hematology, University of Bologna, Via Massarenti 11, 40138, Bologna, Italy.ORCID http://orcid.org/0000-0002-1264-057X
Markus SchmuggeDepartment of Hematology and Oncology, University Children's Hospital, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
Owen SmithDepartment of Paediatric Oncology and Haematology, Our Lady's Children's Hospital Crumlin, Dublin, 12, Ireland.
Jan StaryDepartment of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, V Úvalu 84, 150 06, Prague 5, Czech Republic.
Marek UssowiczDepartment of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University, ul. Borowska 213, 50-556, Wroclaw, Poland.
Marry M van den Heuvel-EibrinkPrincess Maxima Center for Pediatric Oncology, Lundlaan 6, 3584, EA, Utrecht, The Netherlands.
Yassen AssenovComputational Epigenomics Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.
Matthias SchlesnerDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5896-4086
Charlotte NiemeyerDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.
Christian FlothoDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.
Christoph PlassCancer Epigenetics Group, Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany. c.plass@dkfz.de.ORCID http://orcid.org/0000-0003-2554-3952
German Cancer Research Center · DEUniversity of Freiburg · DEHeidelberg University · DEUniversity Medical Center Freiburg · DEAarhus University Hospital · DKCharles University · CZChildren's Health Ireland at Crumlin · IEGhent University Hospital · BEHospital Sant Joan de Déu Barcelona · ESPrincess Máxima Center · NLSt Anna Children's Hospital · ATUniversity Children's Hospital Zurich · CHUniversity of Bologna · ITUniversity of Pavia · ITWroclaw Medical University · PL
Funding
No grant is acknowledged in the PubMed record.
Abstract
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.
Indexed as
DNA MethylationLeukemia, Myelomonocytic, JuvenileNoonan SyndromeProtein Tyrosine Phosphatase, Non-Receptor Type 11Proto-Oncogene Proteins p21(ras)Signal TransductionAntineoplastic AgentsBiopsyChildChild, PreschoolChromatinClinical Trials, Phase III as TopicDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNA Mutational AnalysisAntineoplastic AgentsChromatinDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNMT1 protein, humanKRAS protein, humanProtein Tyrosine Phosphatase, Non-Receptor Type 11Proto-Oncogene Proteins c-cblProto-Oncogene Proteins p21(ras)PTPN11 protein, human
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