PMID- 35081690
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20221018
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 107
IP  - 8
DP  - 2022 Aug 1
TI  - Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin 
      lymphomas: frequency, genetic mechanisms, and clinical significance.
PG  - 1880-1890
LID - 10.3324/haematol.2021.280342 [doi]
AB  - Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are 
      immunomodulatory molecules overexpressed in lymphomas and are promising 
      immunotherapy targets for hematologic malignancies. However, studies of 
      PD-1/PD-L1 overexpression and their clinical significance in aggressive pediatric 
      non-Hodgkin lymphomas (NHL) are limited. We assessed PD-1/PD-L1 overexpression 
      using immunohistochemistry in 68 aggressive pediatric NHL: ALK-positive 
      anaplastic large cell lymphoma (ALK+ ALCL, n=8), Burkitt lymphoma (BL, n=27), and 
      large B-cell lymphoma (LBCL) de novo LBCL, n=22 and diffuse LBCL arising as 
      monomorphic post-transplant lymphoproliferative disorder [PTLD-DLBCL], n=11. In 
      LBCL, correlations between PD-L1 overexpression and Epstein-Barr virus (EBV) 
      status, cell of origin, stage, nodal status, overall survival (OS), and 
      event-free survival (EFS) were examined. The genetic mechanisms of PD-L1 
      overexpression were investigated using targeted next-generation sequencing (NGS) 
      and cytogenetic data. All ALK+ ALCL samples, 50.0% of de novo LBCL (11/22), 72.7% 
      of PTLD-DLBCL (8/11), and no BL overexpressed PD-L1. Overexpressed PD-L1 
      correlated with EBV positivity (P=0.033) in LBCL and lower EFS in de novo LBCL 
      (P=0.017). NGS of select LBCL revealed distinct somatic mutations and an 
      ultra-hypermutated PTLD-DLBCL. Most cases with 9p24.1 copy gains overexpressed 
      PD-L1 although some cases had no discernible genetic drivers of PD-L1 
      overexpression. Overexpressed PD-L1 is common in pediatric LBCL, associated with 
      EBV positivity and 9p24.1 gains, and may have prognostic significance in de novo 
      LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in 
      aggressive pediatric NHL can occur. Thus, additional studies exploring the 
      therapeutic and prognostic significance and molecular mechanisms of PD-L1 
      overexpression in aggressive pediatric NHL are warranted.
FAU - Fisher, Kevin E
AU  - Fisher KE
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas. 
      kevin.fisher@bcm.edu.
FAU - Ferguson, Lizmery S
AU  - Ferguson LS
AD  - Department of Pathology, Texas Children's Hospital, Houston, Texas.
FAU - Coffey, Amy M
AU  - Coffey AM
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas, 
      USA; Clinical Pathology Associates, Austin, Texas.
FAU - Merritt, Brian Y
AU  - Merritt BY
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas.
FAU - Curry, Jonathan L
AU  - Curry JL
AD  - Department of Pathology and Translational Molecular Pathology, Division of 
      Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer 
      Center, Houston, Texas.
FAU - Marcogliese, Andrea N
AU  - Marcogliese AN
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas.
FAU - Major, Angela M
AU  - Major AM
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas.
FAU - Kamdar, Kala Y
AU  - Kamdar KY
AD  - Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer and 
      Hematology Centers, Houston, Texas.
FAU - Lopez-Terrada, Dolores H
AU  - Lopez-Terrada DH
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas, 
      USA; Department of Pediatrics, Baylor College of Medicine, Texas Children's 
      Cancer and Hematology Centers, Houston, Texas.
FAU - Curry, Choladda V
AU  - Curry CV
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, 
      Texas, USA; Department of Pathology, Texas Children's Hospital, Houston, Texas. 
      ccurry@bcm.edu.
LA  - eng
PT  - Journal Article
DEP - 20220801
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Ligands)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Apoptosis
MH  - B7-H1 Antigen/genetics/metabolism
MH  - Child
MH  - *Epstein-Barr Virus Infections/complications/genetics
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Ligands
MH  - *Lymphoma, Large B-Cell, Diffuse/genetics
MH  - *Lymphoma, Large-Cell, Anaplastic
MH  - Programmed Cell Death 1 Receptor/metabolism
MH  - Receptor Protein-Tyrosine Kinases
PMC - PMC9335100
EDAT- 2022/01/28 06:00
MHDA- 2022/08/03 06:00
PMCR- 2022/01/27
CRDT- 2022/01/27 02:31
PHST- 2021/11/12 00:00 [received]
PHST- 2022/01/28 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/01/27 02:31 [entrez]
PHST- 2022/01/27 00:00 [pmc-release]
AID - 10.3324/haematol.2021.280342 [doi]
PST - epublish
SO  - Haematologica. 2022 Aug 1;107(8):1880-1890. doi: 10.3324/haematol.2021.280342.