PMID- 32516416
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20240328
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 11
DP  - 2020 Jun 9
TI  - Gene expression profiling of gray zone lymphoma.
PG  - 2523-2535
LID - 10.1182/bloodadvances.2020001923 [doi]
AB  - Gray zone lymphoma (GZL), a B-cell lymphoma with features intermediate between 
      large B-cell lymphoma (LBCL) and classic Hodgkin lymphoma (cHL), is a rare and 
      poorly defined entity. Alongside GZL, a subset of Epstein-Barr virus 
      (EBV)-positive diffuse large B-cell lymphoma (DLBCL) has been described with 
      polymorphic/GZL-like morphology (polymorphic-EBV-L). To fill the important gap in 
      our understanding of the pathogenic process underlying these entities, we 
      performed a gene expression study of a large international cohort of GZL and 
      polymorphic-EBV-L, combined with cHL and primary mediastinal large B-cell 
      lymphoma (PMBCL) cases. In an unsupervised principal component analysis, GZL 
      cases presented with intermediate scores in a spectrum between cHL and PMBCL, 
      whereas polymorphic-EBV-L clustered distinctly. The main biological pathways 
      underlying the GZL spectrum were related to cell cycle, reflecting tumor cell 
      content, and extracellular matrix signatures related to the cellular tumor 
      microenvironment. Differential expression analysis and phenotypic 
      characterization of the tumor microenvironment highlighted the predominance of 
      regulatory macrophages in GZL compared with cHL and PMBCL. Two distinct subtypes 
      of GZL were distinguishable that were phenotypically reminiscent of PMBCL and 
      DLBCL, and we observed an association of PMBCL-type GZL with clinical 
      presentation in the "thymic" anatomic niche. In summary, gene expression 
      profiling (GEP) enabled us to add precision to the GZL spectrum, describe the 
      biological distinction compared with polymorphic-EBV-L, and distinguish cases 
      with and without thymic involvement as 2 subgroups of GZL, namely PMBCL-like and 
      DLBCL-like GZL.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Sarkozy, Clementine
AU  - Sarkozy C
AD  - INSERM Unite Mixte de Recherche (UMR)-S1052, Centre National de la Recherche UMR 
      5286, Centre de Recherche en Cancerologie de Lyon, Lyon, France.
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Chong, Lauren
AU  - Chong L
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Takata, Katsuyoshi
AU  - Takata K
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Chavez, Elizabeth A
AU  - Chavez EA
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Miyata-Takata, Tomoko
AU  - Miyata-Takata T
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Duns, Gerben
AU  - Duns G
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Telenius, Adele
AU  - Telenius A
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Boyle, Merrill
AU  - Boyle M
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Slack, Graham W
AU  - Slack GW
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Laurent, Camille
AU  - Laurent C
AD  - Institut Universitaire du Cancer-Oncopole de Toulouse, Centre Hospitalier 
      Universitaire Toulouse, INSERM U.1037, Centre de Recherche en Cancerologie de 
      Toulouse-Purpan, Toulouse, France.
FAU - Farinha, Pedro
AU  - Farinha P
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Molina, Thierry J
AU  - Molina TJ
AD  - Pathology Department, Necker Enfants Malades Hospital, Universite Paris 
      Descartes, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France.
FAU - Copie-Bergman, Christiane
AU  - Copie-Bergman C
AD  - Pathology Department, Henri Mondor-Albert Chennevier Hospital, AP-HP, Paris 
      Est-Creteil (UPEC) University, UMR-S 955, INSERM, Creteil, France.
FAU - Damotte, Diane
AU  - Damotte D
AD  - Departement de Pathologie, Groupe Hospitalier Cochin, AP-HP, Paris Descartes 
      University-Sorbonne, Paris, France.
FAU - Salles, Gilles A
AU  - Salles GA
AD  - INSERM Unite Mixte de Recherche (UMR)-S1052, Centre National de la Recherche UMR 
      5286, Centre de Recherche en Cancerologie de Lyon, Lyon, France.
AD  - Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Hematologie, 
      Pierre Benite Cedex, France.
FAU - Mottok, Anja
AU  - Mottok A
AD  - Institute of Human Genetics, Ulm University and Ulm University Medical Center, 
      Ulm, Germany; and.
FAU - Savage, Kerry J
AU  - Savage KJ
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Scott, David W
AU  - Scott DW
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
FAU - Traverse-Glehen, Alexandra
AU  - Traverse-Glehen A
AD  - INSERM Unite Mixte de Recherche (UMR)-S1052, Centre National de la Recherche UMR 
      5286, Centre de Recherche en Cancerologie de Lyon, Lyon, France.
AD  - Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Anatomie 
      Pathologique, Pierre Benite Cedex, France.
FAU - Steidl, Christian
AU  - Steidl C
AD  - Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
LA  - eng
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
SB  - IM
MH  - *Epstein-Barr Virus Infections
MH  - Female
MH  - *Gene Expression Profiling
MH  - Herpesvirus 4, Human/genetics
MH  - *Hodgkin Disease/genetics
MH  - Humans
MH  - *Lymphoma, Large B-Cell, Diffuse/genetics
MH  - Male
MH  - Middle Aged
MH  - Tumor Microenvironment
PMC - PMC7284085
COIS- Conflict-of-interest disclosure: C. Steidl has performed consultancy for Seattle 
      Genetics, Curis Inc., Roche, AbbVie, Juno Therapeutics, and Bayer; and has 
      received research funding from Bristol-Myers Squibb and Trillium Therapeutics 
      Inc. D.W.S. has performed consultancy for Janssen and Celgene; and received 
      research funding from Roche/Genentech, Janssen, and NanoString Technologies. 
      K.J.S. received honoraria and provided consultancy to Bristol-Myers Squibb, 
      Merck, Takeda, Verastem, and Servier. The remaining authors declare no competing 
      financial interests.
EDAT- 2020/06/10 06:00
MHDA- 2021/05/11 06:00
PMCR- 2020/06/09
CRDT- 2020/06/10 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/04/29 00:00 [accepted]
PHST- 2020/06/10 06:00 [entrez]
PHST- 2020/06/10 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/06/09 00:00 [pmc-release]
AID - S2473-9529(20)31279-9 [pii]
AID - 2020/ADV2020001923 [pii]
AID - 10.1182/bloodadvances.2020001923 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Jun 9;4(11):2523-2535. doi: 10.1182/bloodadvances.2020001923.