PD-L1 overexpression correlates with JAK2-V617F mutational burden and is associated with 9p uniparental disomy in myeloproliferative neoplasms.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
23
12
2021
received:
29
11
2021
accepted:
03
01
2022
pubmed:
12
1
2022
medline:
30
4
2022
entrez:
11
1
2022
Statut:
ppublish
Résumé
Myeloproliferative neoplasms (MPN) are chronic stem cell disorders characterized by enhanced proliferation of myeloid cells, immune deregulation, and drug resistance. JAK2 somatic mutations drive the disease in 50-60% and CALR mutations in 25-30% of cases. Published data suggest that JAK2-V617F-mutated MPN cells express the resistance-related checkpoint PD-L1. By applying RNA-sequencing on granulocytes of 113 MPN patients, we demonstrate that PD-L1 expression is highest among polycythemia vera patients and that PD-L1 expression correlates with JAK2-V617F mutational burden (R = 0.52; p < .0001). Single nucleotide polymorphism (SNP) arrays showed that chromosome 9p uniparental disomy (UPD) covers both PD-L1 and JAK2 in all MPN patients examined. MPN cells in JAK2-V617F-positive patients expressed higher levels of PD-L1 if 9p UPD was present compared to when it was absent (p < .0001). Moreover, haplotype-based association analyses provided evidence for germline genetic factors at PD-L1 locus contributing to MPN susceptibility independently of the previously described GGCC risk haplotype. We also found that PD-L1 is highly expressed on putative CD34
Identifiants
pubmed: 35015307
doi: 10.1002/ajh.26461
pmc: PMC9306481
doi:
Substances chimiques
B7-H1 Antigen
0
BRD4 protein, human
0
Cell Cycle Proteins
0
Nuclear Proteins
0
Transcription Factors
0
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
390-400Informations de copyright
© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
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