Disruption of the B-cell specific transcriptional program in HHV-8 associated primary effusion lymphoma cell lines

Arguello, Meztli; Sgarbanti, Marco; Hernandez, Eduardo; Mamane, Yaël; Sharma, Sonia; Servant, Marc J.; Lin, Rongtuan; Hiscott, John

doi:10.1038/sj.onc.1206270

Cited by 48 publications

(47 citation statements)

References 53 publications

(70 reference statements)

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“…Immunoblot analysis of Oct-1, Oct-2, and OCA-B showed normal expression of Oct-1, while levels of Oct-2 and OCA-B were undetectable (Fig. 2D), confirming a previous report (3).…”

Section: Pel Tumor Cells Express Low Levels Of Cigsupporting

confidence: 79%

“…The control of Ig expression is rather complex and involves a diversity of interactions between B-cell-specific factors and regulatory elements (reviewed by Singh, 1994 [61]; Reya and Grosschedl, 1998 [57]; and Henderson and Calame, 1998 [29]). Another of these tissue-restricted factors involved in Ig transcription is PU.1, which is also absent in PEL cells (3). PU.1 is regulated through an octamer motif in its promoter, and its downregulation results from a lack of Oct-2 (3).…”

Section: Discussionmentioning

confidence: 99%

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Role of Defective Oct-2 and OCA-B Expression in Immunoglobulin Production and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation in Primary Effusion Lymphoma

Bartolo

Hyjek

Keller

et al. 2009

J Virol

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Primary effusion lymphoma (PEL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8). Despite having a genotype and gene expression signature of highly differentiated B cells, PEL does not usually express surface or cytoplasmic immunoglobulin (Ig). We show the lack of Oct-2 and OCA-B transcription factors to be responsible, at least in part, for this defect in Ig production. Like Ig genes, ORF50, the key regulator of the switch from latency to lytic reactivation, contains an octamer motif within its promoter. We therefore examined the impact of Oct-2 and OCA-B on ORF50 activation. The binding of Oct-1 to the ORF50 promoter has been shown to significantly enhance ORF50 transactivation. We found that Oct-2, on the other hand, inhibited ORF50 expression and consequently lytic reactivation by competing with Oct-1 for the octamer motif in the ORF50 promoter. Our data suggest that Oct-2 downregulation in infected cells would be favorable to KSHV in allowing for efficient viral reactivation.

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“…Immunoblot analysis of Oct-1, Oct-2, and OCA-B showed normal expression of Oct-1, while levels of Oct-2 and OCA-B were undetectable (Fig. 2D), confirming a previous report (3).…”

Section: Pel Tumor Cells Express Low Levels Of Cigsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Role of Defective Oct-2 and OCA-B Expression in Immunoglobulin Production and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation in Primary Effusion Lymphoma

Bartolo

Hyjek

Keller

et al. 2009

J Virol

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“…Apparently, mutations and translocations of the genes, playing a crucial role in the pathogenesis of non-Hodgkin lymphomas, are rare or absent in cHL. 13 Genomic imbalances or rearrangements are not the causes of PU.1, BOB.1/OBF.1, and OCT2 silencing in cHL. 14 The only known consistent oncogenic feature of cHL, the constitutive nuclear factor (NF)-B activation, can be explained in only a few cases by mutations of a regulatory gene.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma

Ushmorov

Leithäuser

Sakk

et al. 2006

Blood

159

123

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“…80% are EBV ϩ , although LMP1 and LMP2A are barely expressed (10,11). PEL cells have Ig rearrangements but usually lack B cell-typical surface markers, including the BCR (12,13). Reports of BCR Ϫ , KSHV ϩ /EBV Ϫ PEL cells (14,15) raised the question of whether KSHV itself encodes a BCR mimic.…”

mentioning

confidence: 99%

K1 and K15 of Kaposi's Sarcoma-Associated Herpesvirus Are Partial Functional Homologues of Latent Membrane Protein 2A of Epstein-Barr Virus

Steinbrück

Gustems

Medele

et al. 2015

J Virol

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The human herpesviruses Epstein-Barr virus (EBV) and, supporting an essential role of EBV in HL lymphomagenesis (1). EBV ϩ HRS cells express the viral protein latent membrane protein 2A (LMP2A), which can functionally replace the BCR because Ig-negative B cells can only survive if infected with EBV but not with an LMP2A-negative EBV mutant (4). BCR and LMP2A both contain an immunoreceptor tyrosine-based activation motif (ITAM) (5, 6), which is central for the induction of BCR signaling cascades. In contrast to the BCR, LMP2A is thought to be constitutively active and independent of any ligand or antigen encounter (references 7 and 8 and references therein). EBV also encodes LMP1, a constitutive CD40 receptor mimic that provides a second survival signal for B cells. LMP1 together with LMP2A activates HRS cells, protects them from apoptosis, and induces their proliferation (1, 9).PEL tumor cells are infected with KSHV, and ca. 80% are EBV ϩ , although LMP1 and LMP2A are barely expressed (10,11

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Disruption of the B-cell specific transcriptional program in HHV-8 associated primary effusion lymphoma cell lines

Cited by 48 publications

References 53 publications

Role of Defective Oct-2 and OCA-B Expression in Immunoglobulin Production and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation in Primary Effusion Lymphoma

Role of Defective Oct-2 and OCA-B Expression in Immunoglobulin Production and Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation in Primary Effusion Lymphoma

Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma

K1 and K15 of Kaposi's Sarcoma-Associated Herpesvirus Are Partial Functional Homologues of Latent Membrane Protein 2A of Epstein-Barr Virus

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