CD30 in Systemic Mastocytosis

Anrooij, Björn van; Kluin, Philip M.; Elberink, Joanne N.G. Oude; Kluin-Nelemans, Hanneke C.

doi:10.1016/j.iac.2014.01.006

Cited by 21 publications

(12 citation statements)

References 81 publications

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“…[35][36][37][43][44][45][46][47] In an initial report, Sotlar et al described that CD30 is commonly and strongly expressed in the cytoplasm of neoplastic MCs in advanced SM, whereas in most patients with ISM, neoplastic MCs expressed only low amounts or did not exhibit cytoplasmic CD30. 35 In the current study, we were able to confirm that CD30 is expressed in the cytoplasm of neoplastic MCs in advanced SM in most patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Blatt¹,

Cerny-Reiterer

Schwaab

et al. 2015

Blood

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Key Points• In a majority of patients with advanced SM, neoplastic MCs express the target receptor CD30.• The CD30-targeting drug brentuximab-vedotin blocks growth and survival in CD301 neoplastic MCs which favors drug development in advanced SM.The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MCs) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on the surface of neoplastic MCs in advanced SM, and whether this surface structure may serve as therapeutic target in SM. As assessed by flow cytometry, CD30 was found to be expressed on the surface of neoplastic MCs in 3 of 25 patients (12%) with indolent SM, 4 of 7 patients (57%) with aggressive SM, and 4 of 7 patients (57%) with MC leukemia. The immature RAS-transformed human MC line MCPV-1.1 also expressed cell surface CD30, whereas the KIT-transformed MC line HMC-

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Section: Discussionmentioning

confidence: 99%

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Blatt¹,

Cerny-Reiterer

Schwaab

et al. 2015

Blood

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“…CD30 is rarely expressed in normal mast cells, [ 18 ] but frequently expressed in SM. [ 18 – 21 ] CD30 has been found highly expressed in WDSM both by FCI and IHC. [ 4 , 18 ] This is important since WDSM is often negative for CD2 and CD25, and aberrant CD30 expression may be a surrogate marker of mast cell clonality for this variant SM.…”

Section: Discussionmentioning

confidence: 99%

Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities

et al. 2016

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Introduction:Well-differentiated systemic mastocytosis (WDSM) is a rare, recently recognized provisional subvariant of systemic mastocytosis (SM). We report a case of WDSM that showed excellent clinical and cutaneous response to imatinib in the absence of known molecular genetic abnormalities.Clinical Findings/Diagnoses:We present a 24-year-old woman with childhood onset of skin manifestations that progressed to mediator-related systemic events, and a gastrointestinal tract mastocytoma. A subsequent bone marrow examination showed WDSM. Treatment with imatinib resulted in complete resolution of cutaneous lesions and systemic symptoms, which relapsed with the discontinuation of the drug. Targeted next-generation sequencing-based mutation analysis did not demonstrate any mutations in the coding regions of KIT or other genes commonly associated with myeloid neoplasms.Conclusions:The diagnosis of WDSM is challenging in the absence of spindle-shaped mast cells, CD2 or CD25 expression, and KIT D816 mutation. This case illustrated the need for recognizing this unique variant of SM for diagnostic and therapeutic implications.

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“…More recently, new insights into the molecular pathways involved in growth and survival of neoplastic MC has resulted in the identification of new drug targets. One emerging surface target aberrantly expressed on the surface of neoplastic MC is CD30, also known as the Ki‐1 antigen . Recent data suggest that CD30 is expressed in human neoplastic MC and serves as a molecular target in advanced SM .…”

Section: Discussionmentioning

confidence: 99%

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

Bauer

Hadzijusufovic

Cerny-Reiterer

et al. 2016

Vet Comparative Oncology

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CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC.

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CD30 in Systemic Mastocytosis

Cited by 21 publications

References 81 publications

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

Well-differentiated systemic mastocytosis showed excellent clinical response to imatinib in the absence of known molecular genetic abnormalities

IL‐4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

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