Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas Journal Article
| Authors: | Fischer, A.; Albert, T. K.; Moreno, N.; Interlandi, M.; Mormann, J.; Glaser, S.; Patil, P.; de Faria, F. W.; Richter, M.; Verma, A.; Balbach, S. T.; Wagener, R.; Bens, S.; Dahlum, S.; Göbel, C.; Münter, D.; Inserte, C.; Graf, M.; Kremer, E.; Melcher, V.; Di Stefano, G.; Santi, R.; Chan, A.; Dogan, A.; Bush, J.; Hasselblatt, M.; Cheng, S.; Spetalen, S.; Fosså, A.; Hartmann, W.; Herbrüggen, H.; Robert, S.; Oyen, F.; Dugas, M.; Walter, C.; Sandmann, S.; Varghese, J.; Rossig, C.; Schüller, U.; Tzankov, A.; Pedersen, M. B.; d’Amore, F. A.; Mellgren, K.; Kontny, U.; Kancherla, V.; Veloza, L.; Missiaglia, E.; Fataccioli, V.; Gaulard, P.; Burkhardt, B.; Soehnlein, O.; Klapper, W.; de Leval, L.; Siebert, R.; Kerl, K. |
| Article Title: | Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas |
| 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-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- 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-NOSSmarcb1-. 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-NOSSMARCB1- within the TME. © The Author(s) 2024. |
| Keywords: | immunohistochemistry; child; controlled study; human tissue; protein expression; school child; methylation; promoter region; genetics; histone deacetylase inhibitor; nonhuman; comparative study; protein analysis; mouse; animal; metabolism; animals; mice; animal tissue; gene expression; cell growth; protein depletion; animal experiment; animal model; protein; cohort analysis; in vitro study; drug effect; pathology; cell line, tumor; transcriptomics; dna methylation; extracellular matrix; gene expression regulation; lymphocyte differentiation; gene expression regulation, neoplastic; cutaneous t cell lymphoma; peripheral t cell lymphoma; dna; tumor cell line; vorinostat; histone deacetylase inhibitors; cell migration; gene silencing; cell transdifferentiation; tumor; drug therapy; cell interaction; cell communication; rhabdoid tumor; non-hodgkin lymphoma; intracellular space; cell; tumor microenvironment; lymphoma, t-cell, peripheral; drug; single cell analysis; single-cell analysis; epithelial mesenchymal transition; hepatosplenic t cell lymphoma; false discovery rate; t cell prolymphocytic leukemia; angioimmunoblastic t cell lymphoma; smarcb1 protein, human; humans; human; male; female; article; smarcb1 protein; rna sequencing; intestine lymphoma; t cell exhaustion; differential gene expression; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1; single cell rna seq; monomorphic epitheliotropic intestinal t cell lymphoma; smarcb1 protein, mouse |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-10-03 |
| Start Page: | 8571 |
| Language: | English |
| DOI: | 10.1038/s41467-024-52826-0 |
| PUBMED: | 39362842 |
| PROVIDER: | scopus |
| PMCID: | PMC11452211 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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