期刊
BLOOD
卷 118, 期 10, 页码 2659-2669出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-05-326538
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资金
- Cancer Research Society
- Canadian Institutes for Health Research [178536]
- Terry Fox Foundation [019001]
Primary mediastinal large B-cell lymphoma (PMBCL) is a recognized non-Hodgkin lymphoma entity with unique pathologic, clinical, and molecular characteristics distinct from those of other diffuse large B-cell lymphomas. Immunohistochemical characterization and molecular studies strongly suggest that PMBCL is of germinal center or postgerminal center origin. Pivotal gene expression profiling work defined major deregulated pathway activities that overlap with Hodgkin lymphoma and prompted a more detailed analysis of candidate genes. In particular, the nuclear factor-kappa B and the Janus Kinase-Signal Transducer and Activator of Transcription signaling pathways are targeted by multiple genomic hits, and constitutive activity of both pathways can be considered molecular hallmark alterations of PMBCL. Moreover, data are emerging giving unique insight into remodeling of the epigenome that affects transcriptional regulation of a multitude of genes. More recently, the tumor microenvironment of PMBCL has shifted into focus based on a number of gene perturbations altering expression of surface molecules that contribute to immune escape. These findings highlight the importance of immune privilege in the pathogenesis of PMBCL and suggest that disrupting crosstalk between the tumor cells and the microenvironment might be a rational new therapeutic target in conjunction with traditional treatment strategies. (Blood. 2011;118(10):2659-2669)
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