CD30-Induced Signaling Is Absent in Hodgkin's Cells but Present in Anaplastic Large Cell Lymphoma Cells

Hirsch, Burkhard; Hummel, Michael; Bentink, Stefan; Fouladi, Fariba; Spang, Rainer; Zollinger, Raphaël; Stein, Harald; Dürkop, Horst

doi:10.2353/ajpath.2008.070858

Cited by 61 publications

(78 citation statements)

References 42 publications

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“…45,46 Whether CD30 signaling in neoplastic mast cells, like in anaplastic large cell lymphoma cells, triggers NF-kB-mediated increased survival needs to be addressed in further functional studies. 47 The immunohistochemical and molecular demonstration of expression of CD30 by mast cells predominantly in the aggressive variants of mastocytosis may have important consequences for patients with this disease in several respects. First, CD30 can now be regarded as a potential grading marker in systemic mastocytosis that may be useful in screening for advanced disease.…”

Section: Cd30 In Advanced Mastocytosismentioning

confidence: 99%

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

Cerny-Reiterer²,

et al. 2011

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Section: Cd30 In Advanced Mastocytosismentioning

confidence: 99%

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

Cerny-Reiterer²,

et al. 2011

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“…CD30 itself, a cytokine receptor belonging to the tumor necrosis factor receptor superfamily, has been a research focus over the past years, but whether CD30 signaling leads to cell cycle arrest, apoptosis or even proliferation in CD30 + lymphoproliferations is still a matter of debate. [8][9][10][11] We previously showed that a unifying molecular defect in ALCL, regardless of ALK-expression status, was a TCR and CD3ε expression deficiency, which -in most caseswas associated with lost or markedly reduced expression of ZAP-70. 1 The present study had three aims.…”

Section: Cd30mentioning

confidence: 99%

Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations

Geissinger¹,

Sadler²,

Roth³

et al. 2010

Haematologica

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ConclusionsSeverely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30 + lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30 + lymphoproliferations.Key words: systemic and cutaneous CD30 + lymphoproliferations, anaplastic large cell lymphoma, lymphomatoid papulosis, ALCL, LyP, TCR.Citation: Geissinger E, Sadler P, Roth S, Grieb T, Puppe B, Müller N, Reimer P, Vetter-Kauczok CS, Wenzel J, Bonzheim I, Rüdiger T, Müller-Hermelink HK, and Rosenwald A. Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations. Haematologica 20010;95(10):1697-1704. doi:10.3324/haematol.2009 This is an open-access paper. Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30 + T-cell lymphoproliferations © F e r r a t a S t o r t i F o u n d a t i o nIntroduction CD30 + T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALCL) as well as primary cutaneous CD30 + T-cell lymphoproliferative disorders. Morphologically, these entities are characterized by the proliferation of highly atypical, anaplastic CD30 + T cells. Despite the frequent detection of clonally rearranged Tcell receptor (TCR) genes, the expression of T-cell-specific antigens in the tumor cells is not consistently detectable. 1 Systemic ALCL comprise approximately 15% of all peripheral T-cell lymphomas (PTCL) in Europe 2 and are divided into anaplastic lymphoma kinase (ALK) positive and negative subgroups (ALK + and ALK -systemic ALCL), whereas primary cutaneous CD30 + T-cell lymphoproliferative disorders represent a spectrum of skin lesions with diverging and in part overlapping clinical and morphological features. CD30 + T-cell lymphoproliferative disorders include primary cutaneous ALCL, lymphomatoid papulosis and so-called borderline lesions, [3][4][5] but even with the knowledge of the clinical presentation and a detailed morphological and immunohistochemical picture it is sometimes difficult, if not impossible, to classify a particular cutaneous lesion correctly.While the transforming properties of ALK over-expression have been clearly demonstrated ,6,7 the transformation mechanisms in ALK -systemic ALCL and primary cutaneous CD30 + T-cell lymphoproliferative disorders are poorly understood. CD30 itself, a cytokine receptor belonging to the tumor necrosis factor receptor superfamily, has been a research focus over the past years, but whether CD30 signaling lea...

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“…18,19 However, one study showed that CD30 signaling is absent in HRS cells. 20 Therefore, it remains largely unknown how the alternative NF-kB pathway is activated and whether it has a functional role in HRS cell growth and survival.…”

Section: Introductionmentioning

confidence: 99%

Notch is an essential upstream regulator of NF-κB and is relevant for survival of Hodgkin and Reed–Sternberg cells

2011

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A major pathogenetic mechanism in classical Hodgkin lymphoma (cHL) is constitutive activation of canonical nuclear factor-jB (NF-jB) p50/p65 signaling, controlling lymphoma cell proliferation and survival. Recently, we demonstrated that aberrant Notch1 activity is a negative regulator of the B cell program in B cell-derived Hodgkin and Reed-Sternberg (HRS) cells. Despite abundant evidence for a complex contextdependent cross talk between Notch and NF-jB signaling in hematopoietic cells, it is unknown whether these pathways interact in HRS cells. Here, we show that Notch-signaling inhibition in HRS cells by the c-secretase inhibitor (GSI) XII results in decreased alternative p52/RelB NF-jB signaling, interfering with processing of the NF-jB2 gene product p100 into its active form p52. As a result, expression of Notch and NF-jB target genes is reduced, and survival of HRS cells is impaired. Stimulation of alternative NF-jB signaling in the Hodgkin cell line L540cy by activation of the CD30 receptor rescued GSI-mediated loss of cell viability and apoptosis induction. Our data reveal that Notch is an essential upstream regulator of alternative NF-jB signaling and indicate cross talk between both the pathways in HRS cells. Therefore, we suggest that targeting the Notch pathway is a promising therapeutic option in cHL.

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CD30-Induced Signaling Is Absent in Hodgkin's Cells but Present in Anaplastic Large Cell Lymphoma Cells

Cited by 61 publications

References 42 publications

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations

Notch is an essential upstream regulator of NF-κB and is relevant for survival of Hodgkin and Reed–Sternberg cells

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