Expression of B7-2 (CD86) molecules by Reed–Sternberg cells of Hodgkin’s disease

Gool, Stefaan W. Van; Delabie, Jan; Vandenberghe, Peter; Coorevits, Lieve; Wolf‐Peeters, Chris De; Ceuppens, Jan L.

doi:10.1038/sj.leu.2400683

Cited by 23 publications

(17 citation statements)

References 5 publications

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“…69 NF-B-dependent transcriptional regulation of the CD86 promoter has been demonstrated previously. 70 Consistent with previous reports on CD86 expression on malignant cells in lymph node sections, 71,72 CD86 was strongly overexpressed in all H/RS cell lines tested.…”

Section: Discussionsupporting

confidence: 81%

Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

Hinz

Löser

Mathas

et al. 2001

Blood

239

189

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Constitutively activated nuclear factor (NF)- IntroductionNuclear factor (NF)-B transcription factors regulate the expression of numerous genes that are necessary for proper functioning of the immune system and are key mediators of inflammatory responses to pathogens. 1,2 Furthermore, NF-B activity is associated with cell proliferation, transformation, and tumor development. [3][4][5] One of its most important functions is the activation of an antiapoptotic gene expression program. [6][7][8] The NF-B/Rel family consists of 5 members (p50, p52, p65 [RelA], c-Rel, and RelB), which can form various homodimeric or heterodimeric complexes. NF-B is activated by the release from cytoplasmic IB proteins and subsequently translocates into the nucleus. 1,2,9 Activation is triggered by signal-induced phosphorylation of IB␣, IB␤, and IB⑀ at N-terminal serines, which target the inhibitors for rapid degradation by the proteasome. [10][11][12] The IB kinase (IKK) complex, containing 2 protein kinases, IKK␣ and IKK␤, is responsible for the inducible phosphorylation of IBs and is the initial point of convergence for most stimuli that activate 12 Evidence linking aberrant Rel/NF-B activity to oncogenesis has emerged in recent years. Chromosomal rearrangements of genes coding for Rel/NF-B factors have been observed in many human hematopoietic and solid tumors. Several human cancer cell types are characterized by persistent nuclear NF-B activity, as a result of constitutive activation of upstream signaling kinases or mutations inactivating IB subunits. 5 Consistently, the viral oncoprotein v-Rel has transforming capacity in vitro and in vivo, 13 and several oncogenic viruses, such as human T-cell leukemia virus type I and Epstein-Barr virus (EBV), activate NF-B as part of the transformation process. 14,15 Recently, we have discovered deregulated NF-B activation in The molecular basis of constitutive NF-B in H/RS is not completely understood. In some H/RS cell lines and in biopsy samples from patients with relapsed HD, mutations in the IB␣ gene may contribute to constitutive NF-B activation. These mutations produce nonfunctional or unstable IB␣ proteins, missing various portions of the ankyrin domain and the C-terminal region. [22][23][24][25][26] However, most HD cell lines and primary neoplastic cells lack mutations in the ib␣ gene, and constitutive NF-B activity could also be observed in cell lines with wild-type IB␣ alleles. 25 In all cases examined, IKKs were constitutively activated, resulting in rapid degradation of IB␣ proteins and indicating ongoing signal transduction. 25 Because HD is often associated with EBV, the EBV-encoded latent membrane protein-1 may activate NF-B in these cases by promoting IB␣ turnover. 27 However, constitutive IKK activation was also observed in EBV Ϫ cell lines. 25 Interestingly, H/RS cells strongly express CD30 and CD40, 2 members of the tumor necrosis factor (TNF) receptor family that both can activate NF-B. [28][29][30][31][32][33] From the Max Delbrü ck Center for Molecular Medicine; HepaVec...

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Section: Discussionsupporting

confidence: 81%

Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

Hinz

Löser

Mathas

et al. 2001

Blood

239

189

View full text Add to dashboard Cite

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“…Like cHL, MLBCLs also had high levels of expression of the T-helper cell chemokine, RANTES (regulated on activation normal T cells expressed and secreted) ( Table 2) 29 and the costimulatory molecules CD80 (B7.1) and CD86 (B7.2). 34,35 MLBCLs also had increased expression of signaling lymphocytic activation molecule (SLAM), a B-and T-cell surface molecule that potentiates lymphocyte expansion in a CD28-independent manner and serves as a 36 and TIMP1. 37 §Previously identified in MLBCL: FIG1, 21 FAS/Apo1/CD95, 38 MAL, 8,39 and CD58.…”

Section: Il-4-induced Genes Fig1 and Nf-il-3mentioning

confidence: 99%

The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma

Savage

Monti

Kutok

et al. 2003

Blood

771

600

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“…In another study, we analyzed the effects on the expression of costimulatory molecules on ReedSternberg cells for adequate activation of T cells. In spite of the expression of both CD80 [64] and CD86 [65], and of both MHC class I and MHC class II molecules, we could not elicit an autologous T cell response, although the tumor cells could induce an allogeneic T cell response.…”

Section: The Induction Of Antitumoral T Cell Responses Via Cd28 Costimentioning

confidence: 73%

Activation of the immune system in cancer patients

Gool

Hove

Ceuppens

2000

Med. Pediatr. Oncol.

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Expression of B7-2 (CD86) molecules by Reed–Sternberg cells of Hodgkin’s disease

Cited by 23 publications

References 5 publications

Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma

Activation of the immune system in cancer patients

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