دورية أكاديمية
Genetic and phenotypic attributes of splenic marginal zone lymphoma.
| العنوان: | Genetic and phenotypic attributes of splenic marginal zone lymphoma. |
|---|---|
| المؤلفون: | Bonfiglio, F., Bruscaggin, A., Guidetti, F., Terzi di Bergamo, L., Faderl, M., Spina, V., Condoluci, A., Bonomini, L., Forestieri, G., Koch, R., Piffaretti, D., Pini, K., Pirosa, M.C., Cittone, M.G., Arribas, A., Lucioni, M., Ghilardi, G., Wu, W., Arcaini, L., Baptista, M.J., Bastidas, G., Bea, S., Boldorini, R., Broccoli, A., Buehler, M.M., Canzonieri, V., Cascione, L., Ceriani, L., Cogliatti, S., Corradini, P., Derenzini, E., Devizzi, L., Dietrich, S., Elia, A.R., Facchetti, F., Gaidano, G., Garcia, J.F., Gerber, B., Ghia, P., Gomes da Silva, M., Gritti, G., Guidetti, A., Hitz, F., Inghirami, G., Ladetto, M., Lopez-Guillermo, A., Lucchini, E., Maiorana, A., Marasca, R., Matutes, E., Meignin, V., Merli, M., Moccia, A., Mollejo, M., Montalban, C., Novak, U., Oscier, D.G., Passamonti, F., Piazza, F., Pizzolitto, S., Rambaldi, A., Sabattini, E., Salles, G., Santambrogio, E., Scarfò, L., Stathis, A., Stüssi, G., Geyer, J.T., Tapia, G., Tarella, C., Thieblemont, C., Tousseyn, T., Tucci, A., Vanini, G., Visco, C., Vitolo, U., Walewska, R., Zaja, F., Zenz, T., Zinzani, P.L., Khiabanian, H., Calcinotto, A., Bertoni, F., Bhagat, G., Campo, E., De Leval, L., Dirnhofer, S., Pileri, S.A., Piris, M.A., Traverse-Glehen, A., Tzankov, A., Paulli, M., Ponzoni, M., Mazzucchelli, L., Cavalli, F., Zucca, E., Rossi, D. |
| المصدر: | Blood, vol. 139, no. 5, pp. 732-747 |
| سنة النشر: | 2022 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Aged, Animals, Chromosome Aberrations, Female, Humans, Immunophenotyping, Lymphoma, B-Cell, Marginal Zone/diagnosis, Marginal Zone/genetics, Male, Mice, Middle Aged, Multigene Family, Mutation, Spleen/pathology, Splenic Neoplasms/diagnosis, Splenic Neoplasms/genetics, Transcriptome, Tumor Microenvironment |
| الوصف: | Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0006-4971 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34653238; info:eu-repo/semantics/altIdentifier/eissn/1528-0020; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_FF72071F4B1B3; https://serval.unil.ch/notice/serval:BIB_FF72071F4B1BTest; urn:issn:0006-4971; https://serval.unil.ch/resource/serval:BIB_FF72071F4B1B.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_FF72071F4B1B3Test |
| DOI: | 10.1182/blood.2021012386 |
| الإتاحة: | https://doi.org/10.1182/blood.2021012386Test https://serval.unil.ch/notice/serval:BIB_FF72071F4B1BTest https://serval.unil.ch/resource/serval:BIB_FF72071F4B1B.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_FF72071F4B1B3Test |
| حقوق: | info:eu-repo/semantics/openAccess ; Copying allowed only for non-profit organizations ; https://serval.unil.ch/disclaimerTest |
| رقم الانضمام: | edsbas.488EC08D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00064971 |
|---|---|
| DOI: | 10.1182/blood.2021012386 |