Nature Communications (Oct 2024)
Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas
- Anja Fischer,
- Thomas K. Albert,
- Natalia Moreno,
- Marta Interlandi,
- Jana Mormann,
- Selina Glaser,
- Paurnima Patil,
- Flavia W. de Faria,
- Mathis Richter,
- Archana Verma,
- Sebastian T. Balbach,
- Rabea Wagener,
- Susanne Bens,
- Sonja Dahlum,
- Carolin Göbel,
- Daniel Münter,
- Clara Inserte,
- Monika Graf,
- Eva Kremer,
- Viktoria Melcher,
- Gioia Di Stefano,
- Raffaella Santi,
- Alexander Chan,
- Ahmet Dogan,
- Jonathan Bush,
- Martin Hasselblatt,
- Sylvia Cheng,
- Signe Spetalen,
- Alexander Fosså,
- Wolfgang Hartmann,
- Heidi Herbrüggen,
- Stella Robert,
- Florian Oyen,
- Martin Dugas,
- Carolin Walter,
- Sarah Sandmann,
- Julian Varghese,
- Claudia Rossig,
- Ulrich Schüller,
- Alexandar Tzankov,
- Martin B. Pedersen,
- Francesco A. d’Amore,
- Karin Mellgren,
- Udo Kontny,
- Venkatesh Kancherla,
- Luis Veloza,
- Edoardo Missiaglia,
- Virginie Fataccioli,
- Philippe Gaulard,
- Birgit Burkhardt,
- Oliver Soehnlein,
- Wolfram Klapper,
- Laurence de Leval,
- Reiner Siebert,
- Kornelius Kerl
Affiliations
- Anja Fischer
- Institute of Human Genetics, Ulm University Medical Center
- Thomas K. Albert
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Natalia Moreno
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Marta Interlandi
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Jana Mormann
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Selina Glaser
- Institute of Human Genetics, Ulm University Medical Center
- Paurnima Patil
- Institute of Human Genetics, Ulm University Medical Center
- Flavia W. de Faria
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Mathis Richter
- Institute for Experimental Pathology, Center for Molecular Biology of Inflammation, University of Münster
- Archana Verma
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Sebastian T. Balbach
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Rabea Wagener
- Institute of Human Genetics, Ulm University Medical Center
- Susanne Bens
- Institute of Human Genetics, Ulm University Medical Center
- Sonja Dahlum
- Institute of Human Genetics, Ulm University Medical Center
- Carolin Göbel
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, Eppendorf (UKE)
- Daniel Münter
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Clara Inserte
- Institute of Medical Informatics, University of Münster
- Monika Graf
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Eva Kremer
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Viktoria Melcher
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Gioia Di Stefano
- Pathological Anatomy Section, Careggi University Hospital
- Raffaella Santi
- Pathological Anatomy Section, Careggi University Hospital
- Alexander Chan
- Department of Pathology, Hematopathology Service, Memorial Sloan Kettering Cancer Center
- Ahmet Dogan
- Department of Pathology, Hematopathology Service, Memorial Sloan Kettering Cancer Center
- Jonathan Bush
- Division of Anatomical Pathology, British Columbia Children’s Hospital and Women’s Hospital and Health Center
- Martin Hasselblatt
- Institute of Neuropathology, University Hospital Münster
- Sylvia Cheng
- Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, British Columbia Children’s Hospital, University of British Columbia
- Signe Spetalen
- Department of Pathology, Oslo University Hospital
- Alexander Fosså
- Department of Oncology, Oslo University Hospital-Norwegian Radium Hospital
- Wolfgang Hartmann
- Division of Translational Pathology, Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude D17
- Heidi Herbrüggen
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Stella Robert
- Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster
- Florian Oyen
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, Eppendorf (UKE)
- Martin Dugas
- Institute of Medical Informatics, University of Münster
- Carolin Walter
- Institute of Medical Informatics, University of Münster
- Sarah Sandmann
- Institute of Medical Informatics, University of Münster
- Julian Varghese
- Institute of Medical Informatics, University of Münster
- Claudia Rossig
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Ulrich Schüller
- Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, Eppendorf (UKE)
- Alexandar Tzankov
- Institute of Medical Genetics and Pathology, University Hospital Basel
- Martin B. Pedersen
- Department of Hematology, Aarhus University Hospital
- Francesco A. d’Amore
- Department of Hematology, Aarhus University Hospital
- Karin Mellgren
- Department of Pediatric Oncology and Hematology, Sahlgrenska University Hospital, The Queen Silvia Children’s Hospital
- Udo Kontny
- Section of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatric and Adolescent Medicine, RWTH Aachen University Hospital
- Venkatesh Kancherla
- Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital
- Luis Veloza
- Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital
- Edoardo Missiaglia
- Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital
- Virginie Fataccioli
- INSERM U955, Université Paris-Est
- Philippe Gaulard
- Département de Pathologie, Hôpitaux Universitaires Henri Mondor, AP-HP, INSERM U955, Université Paris Est Créteil
- Birgit Burkhardt
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- Oliver Soehnlein
- Institute for Experimental Pathology, Center for Molecular Biology of Inflammation, University of Münster
- Wolfram Klapper
- Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein
- Laurence de Leval
- Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital
- Reiner Siebert
- Institute of Human Genetics, Ulm University Medical Center
- Kornelius Kerl
- Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster
- DOI
- https://doi.org/10.1038/s41467-024-52826-0
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 18
Abstract
Abstract Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS SMARCB1- , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS SMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS Smarcb1- . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS SMARCB1- within the TME.
