Genetic and phenotypic attributes of splenic marginal zone lymphoma

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 o...

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Main Authors:	Bonfiglio, Ferdinando (Author) , Bruscaggin, Alessio (Author) , Guidetti, Francesca (Author) , Terzi di Bergamo, Lodovico (Author) , Faderl, Martin (Author) , Spina, Valeria (Author) , Condoluci, Adalgisa (Author) , Bonomini, Luisella (Author) , Forestieri, Gabriela (Author) , Koch, Ricardo (Author) , Piffaretti, Deborah (Author) , Pini, Katia (Author) , Pirosa, Maria Cristina (Author) , Cittone, Micol Giulia (Author) , Arribas, Alberto (Author) , Lucioni, Marco (Author) , Ghilardi, Guido (Author) , Wu, Wei (Author) , Arcaini, Luca (Author) , Baptista, Maria Joao (Author) , Bastidas, Gabriela (Author) , Bea, Silvia (Author) , Boldorini, Renzo (Author) , Broccoli, Alessandro (Author) , Buehler, Marco Matteo (Author) , Canzonieri, Vincenzo (Author) , Cascione, Luciano (Author) , Ceriani, Luca (Author) , Cogliatti, Sergio (Author) , Corradini, Paolo (Author) , Derenzini, Enrico (Author) , Devizzi, Liliana (Author) , Dietrich, Sascha (Author) , Elia, Angela Rita (Author) , Facchetti, Fabio (Author) , Gaidano, Gianluca (Author) , Garcia, Juan Fernando (Author) , Gerber, Bernhard (Author) , Ghia, Paolo (Author) , Gomes da Silva, Maria (Author) , Gritti, Giuseppe (Author) , Guidetti, Anna (Author) , Hitz, Felicitas (Author) , Inghirami, Giorgio (Author) , Ladetto, Marco (Author) , Lopez-Guillermo, Armando (Author) , Lucchini, Elisa (Author) , Maiorana, Antonino (Author) , Marasca, Roberto (Author) , Matutes, Estella (Author) , Meignin, Veronique (Author) , Merli, Michele (Author) , Moccia, Alden (Author) , Mollejo, Manuela (Author) , Montalban, Carlos (Author) , Novak, Urban (Author) , Oscier, David Graham (Author) , Passamonti, Francesco (Author) , Piazza, Francesco (Author) , Pizzolitto, Stefano (Author) , Rambaldi, Alessandro (Author) , Sabattini, Elena (Author) , Salles, Gilles (Author) , Santambrogio, Elisa (Author) , Scarfò, Lydia (Author) , Stathis, Anastasios (Author) , Stüssi, Georg (Author) , Geyer, Julia T. (Author) , Tapia, Gustavo (Author) , Tarella, Corrado (Author) , Thieblemont, Catherine (Author) , Tousseyn, Thomas (Author) , Tucci, Alessandra (Author) , Vanini, Giorgio (Author) , Visco, Carlo (Author) , Vitolo, Umberto (Author) , Walewska, Renata (Author) , Zaja, Francesco (Author) , Zenz, Thorsten (Author) , Zinzani, Pier Luigi (Author) , Khiabanian, Hossein (Author) , Calcinotto, Arianna (Author) , Bertoni, Francesco (Author) , Bhagat, Govind (Author) , Campo, Elias (Author) , De Leval, Laurence (Author) , Dirnhofer, Stefan (Author) , Pileri, Stefano A. (Author) , Piris, Miguel A. (Author) , Traverse-Glehen, Alexandra (Author) , Tzankov, Alexander (Author) , Paulli, Marco (Author) , Ponzoni, Maurilio (Author) , Mazzucchelli, Luca (Author) , Cavalli, Franco (Author) , Zucca, Emanuele (Author) , Rossi, Davide (Author)
Format:	Article (Journal)
Language:	English
Published:	3 February 2022
In:	Blood Year: 2022, Volume: 139, Issue: 5, Pages: 732-747
ISSN:	1528-0020
DOI:	10.1182/blood.2021012386
Online Access:	Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2021012386
Author Notes:	Ferdinando Bonfiglio, Alessio Bruscaggin, Francesca Guidetti, Lodovico Terzi di Bergamo, Martin Faderl, Valeria Spina, Adalgisa Condoluci, Luisella Bonomini, Gabriela Forestieri, Ricardo Koch, Deborah Piffaretti, Katia Pini, Maria Cristina Pirosa, Micol Giulia Cittone, Alberto Arribas, Marco Lucioni, Guido Ghilardi, Wei Wu, Luca Arcaini, Maria Joao Baptista, Gabriela Bastidas, Silvia Bea, Renzo Boldorini, Alessandro Broccoli, Marco Matteo Buehler, Vincenzo Canzonieri, Luciano Cascione, Luca Ceriani, Sergio Cogliatti, Paolo Corradini, Enrico Derenzini, Liliana Devizzi, Sascha Dietrich, Angela Rita Elia, Fabio Facchetti, Gianluca Gaidano, Juan Fernando Garcia, Bernhard Gerber, Paolo Ghia, Maria Gomes da Silva, Giuseppe Gritti, Anna Guidetti, Felicitas Hitz, Giorgio Inghirami, Marco Ladetto, Armando Lopez-Guillermo, Elisa Lucchini, Antonino Maiorana, Roberto Marasca, Estella Matutes, Veronique Meignin, Michele Merli, Alden Moccia, Manuela Mollejo, Carlos Montalban, Urban Novak, David Graham Oscier, Francesco Passamonti, Francesco Piazza, Stefano Pizzolitto, Alessandro Rambaldi, Elena Sabattini, Gilles Salles, Elisa Santambrogio, Lydia Scarfò, Anastasios Stathis, Georg Stüssi, Julia T. Geyer, Gustavo Tapia, Corrado Tarella, Catherine Thieblemont, Thomas Tousseyn, Alessandra Tucci, Giorgio Vanini, Carlo Visco, Umberto Vitolo, Renata Walewska, Francesco Zaja, Thorsten Zenz, Pier Luigi Zinzani, Hossein Khiabanian, Arianna Calcinotto, Francesco Bertoni, Govind Bhagat, Elias Campo, Laurence De Leval, Stefan Dirnhofer, Stefano A. Pileri, Miguel A. Piris, Alexandra Traverse-Glehen, Alexander Tzankov, Marco Paulli, Maurilio Ponzoni, Luca Mazzucchelli, Franco Cavalli, Emanuele Zucca, and Davide Rossi

MARC


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245	1	0	\|a Genetic and phenotypic attributes of splenic marginal zone lymphoma \|c Ferdinando Bonfiglio, Alessio Bruscaggin, Francesca Guidetti, Lodovico Terzi di Bergamo, Martin Faderl, Valeria Spina, Adalgisa Condoluci, Luisella Bonomini, Gabriela Forestieri, Ricardo Koch, Deborah Piffaretti, Katia Pini, Maria Cristina Pirosa, Micol Giulia Cittone, Alberto Arribas, Marco Lucioni, Guido Ghilardi, Wei Wu, Luca Arcaini, Maria Joao Baptista, Gabriela Bastidas, Silvia Bea, Renzo Boldorini, Alessandro Broccoli, Marco Matteo Buehler, Vincenzo Canzonieri, Luciano Cascione, Luca Ceriani, Sergio Cogliatti, Paolo Corradini, Enrico Derenzini, Liliana Devizzi, Sascha Dietrich, Angela Rita Elia, Fabio Facchetti, Gianluca Gaidano, Juan Fernando Garcia, Bernhard Gerber, Paolo Ghia, Maria Gomes da Silva, Giuseppe Gritti, Anna Guidetti, Felicitas Hitz, Giorgio Inghirami, Marco Ladetto, Armando Lopez-Guillermo, Elisa Lucchini, Antonino Maiorana, Roberto Marasca, Estella Matutes, Veronique Meignin, Michele Merli, Alden Moccia, Manuela Mollejo, Carlos Montalban, Urban Novak, David Graham Oscier, Francesco Passamonti, Francesco Piazza, Stefano Pizzolitto, Alessandro Rambaldi, Elena Sabattini, Gilles Salles, Elisa Santambrogio, Lydia Scarfò, Anastasios Stathis, Georg Stüssi, Julia T. Geyer, Gustavo Tapia, Corrado Tarella, Catherine Thieblemont, Thomas Tousseyn, Alessandra Tucci, Giorgio Vanini, Carlo Visco, Umberto Vitolo, Renata Walewska, Francesco Zaja, Thorsten Zenz, Pier Luigi Zinzani, Hossein Khiabanian, Arianna Calcinotto, Francesco Bertoni, Govind Bhagat, Elias Campo, Laurence De Leval, Stefan Dirnhofer, Stefano A. Pileri, Miguel A. Piris, Alexandra Traverse-Glehen, Alexander Tzankov, Marco Paulli, Maurilio Ponzoni, Luca Mazzucchelli, Franco Cavalli, Emanuele Zucca, and Davide Rossi
264		1	\|c 3 February 2022
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500			\|a Prepublished online on Blood First Edition 15 October 2021
500			\|a Gesehen am 08.07.2022
520			\|a 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 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.
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JSO			\|a ergio Cogliatti, Paolo Corradini, Enrico Derenzini, Liliana Devizzi, Sascha Dietrich, Angela Rita Elia, Fabio Facchetti, Gianluca Gaidano, Juan Fernando Garcia, Bernhard Gerber, Paolo Ghia, Maria Gomes da Silva, Giuseppe Gritti, Anna Guidetti, Felicitas Hitz, Giorgio Inghirami, Marco Ladetto, Armando Lopez-Guillermo, Elisa Lucchini, Antonino Maiorana, Roberto Marasca, Estella Matutes, Veronique Meignin, Michele Merli, Alden Moccia, Manuela Mollejo, Carlos Montalban, Urban Novak, David Graham Oscier, Francesco Passamonti, Francesco Piazza, Stefano Pizzolitto, Alessandro Rambaldi, Elena Sabattini, Gilles Salles, Elisa Santambrogio, Lydia Scarfò, Anastasios Stathis, Georg Stüssi, Julia T. Geyer, Gustavo Tapia, Corrado Tarella, Catherine Thieblemont, Thomas Tousseyn, Alessandra Tucci, Giorgio Vanini, Carlo Visco, Umberto Vitolo, Renata Walewska, Francesco Zaja, Thorsten Zenz, Pier Luigi Zinzani, Hossein Khiabanian, Arianna Calcinotto, Francesco Bertoni, Govind Bhagat, Elias Campo, Laurence De Leval, Stefan Dirnhofer, Stefano A. Pileri, Miguel A. Piris, Alexandra Traverse-Glehen, Alexander Tzankov, Marco Paulli, Maurilio Ponzoni, Luca Mazzucchelli, Franco Cavalli, Emanuele Zucca, and Davide Rossi"]},"id":{"doi":["10.1182/blood.2021012386"],"eki":["180947809X"]},"relHost":[{"language":["eng"],"note":["Gesehen am 21.04.2023"],"type":{"bibl":"periodical","media":"Online-Ressource"},"origin":[{"publisherPlace":"Washington, DC ; Philadelphia, Pa. ; Stanford, Calif.","dateIssuedDisp":"1946-","publisher":"American Society of Hematology ; Saunders ; HighWire Press","dateIssuedKey":"1946"}],"titleAlt":[{"title":"Blood online"}],"title":[{"title_sort":"Blood","subtitle":"journal of the American Society of Hematology","title":"Blood"}],"part":{"issue":"5","text":"139(2022), 5, Seite 732-747","pages":"732-747","year":"2022","volume":"139","extent":"16"},"corporate":[{"role":"isb","display":"American Society of Hematology"}],"disp":"Genetic and phenotypic attributes of splenic marginal zone lymphomaBlood","id":{"zdb":["1468538-3"],"eki":["266886647"],"issn":["1528-0020"]},"pubHistory":["1.1946 -"],"recId":"266886647","physDesc":[{"extent":"Online-Ressource"}]}]}
SRT			\|a BONFIGLIOFGENETICAND3202

Genetic and phenotypic attributes of splenic marginal zone lymphoma

MARC

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