Publications

Authors:

Bonfiglio, Ferdinando; Bruscaggin, Alessio; Guidetti, Francesca; Terzi di Bergamo, Lodovico; Faderl, Martin; Spina, Valeria; Condoluci, Adalgisa; Bonomini, Luisella; Forestieri, Gabriela; Koch, Ricardo; Piffaretti, Deborah; Pini, Katia; Pirosa, Maria Cristina; Cittone, Micol Giulia; Arribas, Alberto; Lucioni, Marco; Ghilardi, Guido; Wu, Wei; Arcaini, Luca; Baptista, Maria Joao; Bastidas, Gabriela; Bea, Silvia; Boldorini, Renzo; Broccoli, Alessandro; Buehler, Marco Matteo; Canzonieri, Vincenzo; Cascione, Luciano; Ceriani, Luca; Cogliatti, Sergio; Corradini, Paolo; Derenzini, Enrico; Devizzi, Liliana; Dietrich, Sascha; Elia, Angela Rita; Facchetti, Fabio; Gaidano, Gianluca; Garcia, Juan Fernando; Gerber, Bernhard; Ghia, Paolo; Gomes da Silva, Maria; Gritti, Giuseppe; Guidetti, Anna; Hitz, Felicitas; Inghirami, Giorgio; Ladetto, Marco; Lopez-Guillermo, Armando; Lucchini, Elisa; Maiorana, Antonino; Marasca, Roberto; Matutes, Estella; Meignin, Veronique; Merli, Michele; Moccia, Alden; Mollejo, Manuela; Montalban, Carlos; Novak, Urban; Oscier, David Graham; Passamonti, Francesco; Piazza, Francesco; Pizzolitto, Stefano; Rambaldi, Alessandro; Sabattini, Elena; Salles, Gilles; Santambrogio, Elisa; Scarfò, Lydia; Stathis, Anastasios; Stüssi, Georg; Geyer, Julia T; Tapia, Gustavo; Tarella, Corrado; Thieblemont, Catherine; Tousseyn, Thomas; Tucci, Alessandra; Vanini, Giorgio; Visco, Carlo; Vitolo, Umberto; Walewska, Renata; Zaja, Francesco; Zenz, Thorsten; Zinzani, Pier Luigi; Khiabanian, Hossein; Calcinotto, Arianna; Bertoni, Francesco; Bhagat, Govind; Campo, Elias; De Leval, Laurence; Dirnhofer, Stefan; Pileri, Stefano A; Piris, Miguel A; Traverse-Glehen, Alexandra; Tzankov, Alexander; Paulli, Marco; Ponzoni, Maurilio; Mazzucchelli, Luca; Cavalli, Franco; Zucca, Emanuele; Rossi, Davide

Title:

Genetic and phenotypic attributes of splenic marginal zone lymphoma

Year:

2022

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

Blood

ISSN of journal:

0006-4971

N° Volume:

139

Number or Folder:

5

:

American Society of Hematology

Page numbers:

732-747

Keyword:

Aged; Animals; Chromosome Aberrations; Female; Humans; Immunophenotyping; Lymphoma, B-Cell, Marginal Zone; Male; Mice; Middle Aged; Multigene Family; Mutation; Spleen; Splenic Neoplasms; Transcriptome; Tumor Microenvironment

Short description of contents:

: 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.

Product ID:

126832

Handle IRIS:

11562/1064983

Last Modified:

January 23, 2025

Bibliographic citation:

Bonfiglio, Ferdinando; Bruscaggin, Alessio; Guidetti, Francesca; Terzi di Bergamo, Lodovico; Faderl, Martin; Spina, Valeria; Condoluci, Adalgisa; Bonomini, Luisella; Forestieri, Gabriela; Koch, Ricardo; Piffaretti, Deborah; Pini, Katia; Pirosa, Maria Cristina; Cittone, Micol Giulia; Arribas, Alberto; Lucioni, Marco; Ghilardi, Guido; Wu, Wei; Arcaini, Luca; Baptista, Maria Joao; Bastidas, Gabriela; Bea, Silvia; Boldorini, Renzo; Broccoli, Alessandro; Buehler, Marco Matteo; Canzonieri, Vincenzo; Cascione, Luciano; Ceriani, Luca; Cogliatti, Sergio; Corradini, Paolo; Derenzini, Enrico; Devizzi, Liliana; Dietrich, Sascha; Elia, Angela Rita; Facchetti, Fabio; Gaidano, Gianluca; Garcia, Juan Fernando; Gerber, Bernhard; Ghia, Paolo; Gomes da Silva, Maria; Gritti, Giuseppe; Guidetti, Anna; Hitz, Felicitas; Inghirami, Giorgio; Ladetto, Marco; Lopez-Guillermo, Armando; Lucchini, Elisa; Maiorana, Antonino; Marasca, Roberto; Matutes, Estella; Meignin, Veronique; Merli, Michele; Moccia, Alden; Mollejo, Manuela; Montalban, Carlos; Novak, Urban; Oscier, David Graham; Passamonti, Francesco; Piazza, Francesco; Pizzolitto, Stefano; Rambaldi, Alessandro; Sabattini, Elena; Salles, Gilles; Santambrogio, Elisa; Scarfò, Lydia; Stathis, Anastasios; Stüssi, Georg; Geyer, Julia T; Tapia, Gustavo; Tarella, Corrado; Thieblemont, Catherine; Tousseyn, Thomas; Tucci, Alessandra; Vanini, Giorgio; Visco, Carlo; Vitolo, Umberto; Walewska, Renata; Zaja, Francesco; Zenz, Thorsten; Zinzani, Pier Luigi; Khiabanian, Hossein; Calcinotto, Arianna; Bertoni, Francesco; Bhagat, Govind; Campo, Elias; De Leval, Laurence; Dirnhofer, Stefan; Pileri, Stefano A; Piris, Miguel A; Traverse-Glehen, Alexandra; Tzankov, Alexander; Paulli, Marco; Ponzoni, Maurilio; Mazzucchelli, Luca; Cavalli, Franco; Zucca, Emanuele; Rossi, Davide, Genetic and phenotypic attributes of splenic marginal zone lymphoma «Blood» , vol. 139 , n. 5 , 2022 , pp. 732-747

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo