CD30+ lymphoproliferative disorders

Leval, Laurence de; Gaulard, Philippe

doi:10.3324/haematol.2010.029256

Cited by 33 publications

(26 citation statements)

References 22 publications

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“…In pathological conditions, CD30 expression is found at various concentrations in different lymphomas of B cell or T cell derivation, and also in several reactive conditions (table 1) [3]. Strong and homogenous CD30 expression by neoplastic cells occurs primarily in three groups: classical Hodgkin lymphoma, systemic ALCL and primary cutaneous CD30-positive T cell lymphoproliferative disorders [1,4,5].…”

Section: Cd30 Expression and Detectionmentioning

confidence: 99%

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Targeting CD30 in Malignant Tissues: Challenges in Detection and Clinical Applications

Wasik

Jimenez²,

Weisenburger

2013

Pathobiology

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The CD30 transmembrane receptor from the tumor necrosis factor receptor family is expressed in a distinct, yet diverse set of lymphoproliferative disorders and a small subset of normal activated lymphocytes. Therefore, detection of CD30 expression when performed properly according to the standardized methods facilitates diagnosis of Hodgkin lymphoma, anaplastic large cell lymphoma, and other disorders expressing the receptor. More recently, CD30 has also become an attractive therapeutic target. The preliminary observations indicate that the methods currently used to detect CD30 expression, typically immunohistochemistry performed on formalin-fixed, paraffin-embedded tissues, may be suboptimal in regard to identifying CD30 as a therapeutic target since only a limited number of CD30 receptor molecules per cell may be sufficient to achieve therapeutic effect.

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Section: Cd30 Expression and Detectionmentioning

confidence: 99%

“…Because CD30 is not found in most normal tissues outside of the immune system or on resting monocytes or lymphocytes, it provides an ideal target for immunotherapy [1,2,3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Targeting CD30 in Malignant Tissues: Challenges in Detection and Clinical Applications

Wasik

Jimenez²,

Weisenburger

2013

Pathobiology

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“…Our findings establish that the defective expression of TCR-related signaling molecules is also a characteristic feature of CD30 + PTCL, NOS, thus pointing towards the impairment of TCR signaling as a pathway common to all CD30 + PTCL, including NOS cases, and raising consideration of whether the up-regulation of CD30 and disturbed expression of TCR-associated molecules might be mechanistically related. 33 …”

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confidence: 99%

CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features

et al. 2013

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Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30 + peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30 + and CD30 -; anaplastic large cell lymphomas, ALK + and ALK -), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30 -tumors, CD30+ peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK -anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30+ peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30 -samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30-peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30 + subgroups. In conclusion, we show molecular and phenotypic features common to CD30 + peripheral T-cell lymphomas, and significant differences between CD30 -and CD30 + peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups. CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features

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“…71 As discussed above, the anti-CD30 immunoconjugate BV has shown impressive activity in relapsed/refractory ALCL. Its role is being evaluated in other CD30-expressing PTCL subtypes and correlation of activity with CD30 expression will be interesting.…”

Section: Biomarker-directed Therapymentioning

confidence: 99%

New Therapies in T-cell Lymphoma

2014

Lymphoma and Chronic Lymphocytic Leukemias

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T-cell lymphomas represent 10-12% of all patients with non-Hodgkin lymphoma (NHL) in the Western world. When cutaneous T-cell lymphoma (CTCL) is excluded, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL) represent the overwhelming majority of patients in this population. These diseases remain a great challenge to treat. They are characterized by an aggressive presentation, extranodal disease, paraneoplastic phenomena, and resistance to standard chemotherapeutics. With the rapid development of new molecular gene profiling techniques, it is highly likely that these diseases will be subclassified by molecular abnormalities in the future. An evolving understanding of the tumor molecular pathogenesis will undoubtedly lead to further novel targeted therapies. Immunoconjugates, such as brentuximab vedotin (BV), have provided outstanding responses in relapsed, refractory CD30-positive ALCL. Histone deacetylase (HDAC) inhibitors have shown activity in PTCL and are potentially synergistic with proteasome inhibitors. Denileukin diftitox is an interesting recombinant DNA fusion protein linking fragments of the diphtheria toxin to interleukin-2 (IL-2) that is tested in clinical trials. Crizotinib, a highly specific anaplastic lymphoma kinase (ALK) inhibitor, has shown great promise in small number of patients with ALK-positive ALCL; the future of patients with this disorder looks very promising. Biomarker-driven chemotherapeutics is becoming a critical part of the state-of-the-art treatment in early-and late-phase clinical trials. It is crucial that future trials include sensible biomarker-based designs when future treatments are used in these challenging disorders.KEY WORDS: T cell lymphoma, angioimmunoplastic lymphoma, anaplastic large cell lymphoma, brentuximab, crizotinib disclose no potential conflicts of interest.COPYRIGHT: © the authors, publisher and licensee Libertas academica Limited. this is an open-access article distributed under the terms of the Creative Commons CC-By-nC 3.0 License. CORRESPONDENCE: graham.collins@ouh.nhs.uk this paper was subject to independent, expert peer review by a minimum of two blind peer reviewers. all editorial decisions were made by the independent academic editor. all authors have provided signed confirmation of their compliance with ethical and legal obligations including (but not limited to) use of any copyrighted material, compliance with ICMJE authorship and competing interests disclosure guidelines and, where applicable, compliance with legal and ethical guidelines on human and animal research participants. provenance: the authors were invited to submit this paper.

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CD30+ lymphoproliferative disorders

Cited by 33 publications

References 22 publications

Targeting CD30 in Malignant Tissues: Challenges in Detection and Clinical Applications

Targeting CD30 in Malignant Tissues: Challenges in Detection and Clinical Applications

CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features

New Therapies in T-cell Lymphoma

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