High expression of CD30 and JunB is the hallmark of malignant cells in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Ligand-independent signaling by CD30 induces JunB, which activates the CD30 promoter, stabilizing CD30 expression and supporting the survival of Hodgkin-Reed-Sternberg (H-RS) and ALCL cells. Here we show for the first time CpG islands encompassing 60 CpG dinucleotides, located in the core promoter, exon 1 and intron 1 of CD30 gene. Analysis of the methylation status of CD30 CpG islands in H-RS, ALCL and unrelated cell lines reveals an inverse relationship between the extent of CD30 CpG methylation and CD30 expression. CD30 CpG islands of H-RS and ALCL cell lines are rarely methylated. Methylation of the CD30 promoter decreases CD30 induction and JunB action on the demethylated CD30 promoter enhances CD30 induction. CD30 and JunB are strongly expressed in H-RS and ALCL cells, whereas they are not expressed in nonmalignant lymphocytes in which CD30 CpG islands are rarely methylated. We conclude that constitutive action of aberrantly expressed JunB on hypomethylated CD30 CpG islands of lymphocytes triggers CD30 induction and initiates activation of the JunB-CD30-JunB loop, essential to the pathogenesis of HL and ALCL.
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http://dx.doi.org/10.1038/labinvest.3700696 | DOI Listing |
Nat Commun
May 2020
Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4 CD44 CD62L PD-1 CD153 cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice.
View Article and Find Full Text PDFFront Immunol
August 2017
INSERM U976, Hôpital Saint-Louis, Paris, France.
KIR3DL2 is a member of the killer cell immunoglobulin-like receptor (KIR) family that was initially identified at the surface of natural killer (NK) cells. KIR3DL2, also known as CD158k, is expressed as a disulfide-linked homodimer. Each chain is composed of three immunoglobulin-like domains and a long cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs.
View Article and Find Full Text PDFJ Invest Dermatol
April 2015
Servei de Dermatologia, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address:
MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID.
View Article and Find Full Text PDFBlood
May 2014
Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China;
Cutaneous CD30(+) lymphoproliferative disease (CD30(+)LPD), characterized by the presence of CD30(+) anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). However, little is known about the pathobiology of the CD30(+) lymphoma cells, as well as the mechanisms of disease progression. Here we report that Special AT-rich region binding protein 1 (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30(+) lymphoma cells in most CD30(+)LPDs, and its expression is upregulated during disease progression.
View Article and Find Full Text PDFPoult Sci
July 2012
Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.
Epigenetic modification is widely known to be involved in embryo development, aging, tumorigenesis, and many complex diseases. Both hypermethylation of CpG islands at the gene promoters and global hypomethylation are involved in the initiation and progression of carcinogenesis. However, only a small portion of hypomethylation occurs at gene promoters and leads to the overexpression of certain oncogenes.
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