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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
RNA and protein expression of Herpesvirus Entry Mediator (HVEM) is associated with molecular markers, immunity-related pathways and relapse-free survival of patients with AML.
Cancer Immunol. Immunother. 64, 1505-1515 (2015)
Immune checkpoint molecules are highly relevant as potential prognostic markers and therapeutic targets in malignant diseases. HVEM belongs to the TNF receptor family and provides stimulatory as well as inhibitory signals depending on the ligand. Abnormal HVEM expression has been described in various malignancies, but the role in AML is unknown. Here we report extensive data on HVEM surface protein expression analyzed by flow cytometry on bone marrow leukemic cells of 169 AML patients at diagnosis. An independent cohort of 512 AML patients was analyzed for HVEM mRNA expression in bone marrow samples by Affymetrix microarrays. Consistently for both cohorts and methods, we show that HVEM was differentially expressed and that expression levels were associated with defined genetic markers. HVEM expression was lower in cases with FLT3-ITD (p = 0.001, p < 0.001), with mutations in NPM1 (p = 0.001, p < 0.001) or with the combination of NPM1 mutation and FLT3 wild type (p = 0.049, p = 0.050), while a biallelic mutation in CEBPA correlated positively with higher HVEM expression (p = 0.015, p < 0.001). In a differential gene expression analysis, we found 13 genes including HOXA9, MEIS1 and MN1 that were closely associated with HVEM expression. Besides, four gene sets closely linked to immunity were enriched in HVEMhigh samples. Finally, high expression of HVEM was associated with a trend toward longer relapse-free survival. The results of this study provide new information on the potential significance of HVEM in AML.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Acute Myeloid Leukemia (aml) ; Costimulation ; Gene Expression Analysis ; Herpesvirus Entry Mediator (hvem) ; Immune Checkpoint Molecules ; Immunophenotyping
ISSN (print) / ISBN
0340-7004
e-ISSN
1432-0851
Zeitschrift
Cancer Immunology, Immunotherapy
Quellenangaben
Band: 64,
Heft: 12,
Seiten: 1505-1515
Verlag
Springer
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Hematopoetic Cell Transplants (IMI-KHZ)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)