ArticleNature genetics2015
Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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142citing papers in PubMed, 1 pooled it
17.2field-weighted citation impact, top 1% of its field
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- [Chinese guideline for diagnosis and treatment of adult acute lymphoblastic leukemia (2024)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Guideline
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- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- The case for targeting enhancer regions in high-risk TCF3::HLF-positive B-cell acute lymphoblastic leukemia.HemaSphere · 2026Article
- TCF3::HLF-positive B-ALL: integrated clinical and molecular characterization of 34 cases from a single-center cohort.British journal of cancer · 2026Article
- ZNF184 negatively regulates HR repair and predicts poor prognosis in acute lymphoblastic leukemia.Nucleic acids research · 2026Article
- TCF3::HLF orchestrates an enhancer-promoter network with activation of MEF2C to promote immature HSC gene expression in leukemia.Science advances · 2026Article
- Donor-derived CD19-targeted CAR-NK cells induce complete remission in a child with relapsed B-ALL after failure of blinatumomab and autologous CD19-targeted CAR-T.Journal for immunotherapy of cancer · 2026Article
- Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026Review
- Toward chemotherapy-reduced cure forHaematologica · 2026Article
- ELDA: real-time functional drug profiling in acute lymphoblastic leukemia.Frontiers in oncology · 2026Article
- Durable remission achieved in pediatric patients withHaematologica · 2026Article
- Analysis of the therapeutic effect of allogeneic hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia withTranslational pediatrics · 2025Article
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- Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF.Human cell · 2025Article
- Insights into the Prognostic Value of Telomere Length in Childhood Acute Lymphoblastic Leukemia.Life (Basel, Switzerland) · 2025Article
- An antibody-drug conjugate targeting VpreB1 for the treatment of B-cell acute lymphoblastic leukemia.Blood neoplasia · 2025Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Review
82 more citing papers are in PubMed but not listed here.
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Authors and funding
67 authors at 20 institutions in 9 countries.
Ute Fischer *Clinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Michael Forster *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Anna Rinaldi *Pediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Thomas Risch *Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Stéphanie Sungalee *European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Hans-Jörg Warnatz *Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Beat BornhauserPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Michael GombertClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Christina KratschDepartment of Algorithmic Bioinformatics, Heinrich-Heine-University, Düsseldorf, Germany.
Adrian M StützEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Marc SultanDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Joelle TchindaPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Catherine L WorthDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Vyacheslav AmstislavskiyDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nandini BadarinarayanInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
André BaruchelDepartment of Pediatric Hemato-Immunology, Hôpital Robert Debré and Paris Diderot University, Paris, France.
Thies BartramDepartment of Pediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Giuseppe BassoDepartment of Pediatrics, Laboratory of Pediatric Hematology/Oncology, University of Padova, Padova, Italy.
Cengiz CanpolatDepartment of Pediatrics, Acıbadem University Medical School, Ataşehir, Istanbul, Turkey.
Gunnar CarioDepartment of Pediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Hélène CavéDepartment of Genetics, Hôpital Robert Debré and Paris Diderot University, Paris, France.
Dardane DakajPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Mauro DelorenziLudwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland.
Maria Pamela DobaySwiss Institute for Bioinformatics (SIB), Lausanne, Switzerland.
Cornelia EckertPediatric Hematology and Oncology, Charité University Hospital, Berlin, Germany.
Eva EllinghausInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Sabrina EugsterPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Viktoras FrismantasPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Sebastian GinzelClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Oskar A HaasChildren's Cancer Research Institute, Vienna, Austria.
Olaf HeidenreichNorthern Institute of Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
Georg Hemmrich-StanisakInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Kebria HezavehClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Jessica I HöllClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Sabine HornhardtFederal Office for Radiation Protection, Oberschleissheim, Germany.
Peter HusemannClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Priyadarshini KachrooInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Christian P KratzPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Geertruy Te KronnieDepartment of Pediatrics, Laboratory of Pediatric Hematology/Oncology, University of Padova, Padova, Italy.
Blerim MarovcaPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Felix NiggliPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Alice C McHardyDepartment of Algorithmic Bioinformatics, Heinrich-Heine-University, Düsseldorf, Germany.
Anthony V MoormanNorthern Institute of Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
Renate Panzer-GrümayerChildren's Cancer Research Institute, Vienna, Austria.
Britt S PetersenInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Benjamin RaederEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Meryem RalserDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Philip RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Daniel SchäferClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Martin SchrappeDepartment of Pediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Moritz SchütteAlacris Theranostics GmbH, Berlin, Germany.
Björn StadeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Ralf ThieleDepartment of Computer Science, Bonn-Rhine-Sieg University of Applied Sciences, Sankt Augustin, Germany.
Nicolas von der WeidUniversitäts-Kinderspital beider Basel (UKBB), Basel, Switzerland.
Ajay VoraSheffield Children's Hospital, Sheffield, United Kingdom.
Marketa ZaliovaPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Langhui ZhangClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Thomas ZichnerEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Martin ZimmermannPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Hans LehrachDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Arndt BorkhardtClinic for Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Jean-Pierre BourquinPediatric Oncology, Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Jan O KorbelEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Martin StanullaPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Marie-Laure YaspoDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Christian-Albrechts-Universität zu Kiel · DEHeinrich Heine University Düsseldorf · DEUniversity Children's Hospital Zurich · CHMax Planck Institute for Molecular Genetics · DEEuropean Molecular Biology Laboratory · DEMedizinische Hochschule Hannover · DEHochschule Bonn-Rhein-Sieg · DEInstitute of Cancer Research · GBSIB Swiss Institute of Bioinformatics · CHSt Anna Children's Hospital · ATUniversité Paris Cité · FRUniversity of Padua · ITAlacris (Germany) · DECharité - Universitätsmedizin Berlin · DECharles University · CZFederal Office for Radiation Protection · DEFujian Medical University · CNIstanbul University · TRSheffield Children's Hospital · GBUniversity Children’s Hospital Basel · CH
Funding
Cancer Research UK 12788European Research Council 336045
Abstract
TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease.
Indexed as
AnimalsAntineoplastic AgentsCoculture TechniquesCohort StudiesDNA Mutational AnalysisDrug Resistance, NeoplasmFemaleGene ExpressionGenetic Association StudiesGenomicsHumansImmunoglobulin Light Chains, SurrogateInhibitory Concentration 50Kaplan-Meier EstimateMaleMice, Inbred NODAntineoplastic AgentsImmunoglobulin Light Chains, SurrogateOncogene Proteins, FusionPAX5 protein, humanPAX5 Transcription FactorTCF3-HLF fusion protein, humanVPREB1 protein, human
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