DOCSLIB.ORG

Relation of CD30 Expression to Survival and Morphology in Large Cell B Cell Lymphomas J Clin Pathol: First Published As 10.1136/Jcp.47.1.33 on 1 January 1994

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Relation of CD30 Expression to Survival and Morphology in Large Cell B Cell Lymphomas J Clin Pathol: First Published As 10.1136/Jcp.47.1.33 on 1 January 1994 J Clin Pathol 1994;47:33-37 33 Relation of CD30 expression to survival and morphology in large cell B cell lymphomas J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994. Downloaded from L A Noorduyn, P C de Bruin, P van Heerde, M M van de Sandt, G J Ossenkoppele, CJLMMeijer Abstract the nerve growth factor receptor superfamily.3 Aims-To investigate whether CD30 Because these CD30 positive lymphomas expression is correlated with anaplastic seemed to present a specific histological pic- morphology, and whether this correlated ture, this group of lymphomas was called with a better survival in large cell B cell anaplastic large cell (Ki-I +) lymphoma, and lymphomas, as has been described for was incorporated in the updated version of T cell lymphomas. the Kiel classification among the high grade Methods-CD30 expression was investi- category of both B cell and T cell gated using frozen sections in a series of lymphomas.4 Several reports have described 146 large cell B cell lymphomas. Clinical cases or series of these anaplastic large cell data and follow up information were col- lymphomas, most of which have concentrated lected from 25 lymphomas with strong on the T cell variety.2 5 Furthermore, CD30 expression, 30 lymphomas with several morphological subtypes have been partial CD30 expression, and a control described.5 7 17-20 group of 25 lymphomas which did not According to the updated Kiel classifica- express CD30. tion, a lymphoma should not only express Results-Morphological distinction between CD30, but also exhibit a so-called "anaplas- anaplastic and non-anaplastic tumours tic" morphology, to qualify as an anaplastic was difficult. Of the cases with an large cell lymphoma. Some studies mention anaplastic morphology, 50% were CD30 the expression of CD30 in non-anaplastic positive, as were 24% of the polymorphic lymphomas,2782' but none of these studies centroblastic B cell lymphomas. Only has systematically addressed the question of 65% of the morphologically non-anaplas- how frequently CD30 expression occurs in tic tumours were completely CD30 nega- different morphological subtypes of large cell tive. There was no difference in survival non-Hodgkin's lymphoma. In T cell among patients with lymphomas express- lymphomas the relation between anaplastic ing CD30 and those that did not. Patients morphology and CD30 expression seems to http://jcp.bmj.com/ with morphologically anaplastic B cell be fairly good,22 and CD30 expression is lymphomas did not differ in their sur- associated with a relatively benign clinical vivals from those with other high grade B course.22 23 Whether this also holds true for B cell lymphomas. Clinical stage at presen- cell lymphomas is presently unknown. tation was the only variable that was sig- nificantly associated with survival. Department of Conclusions-CD30 expression occurs Methods on October 2, 2021 by guest. Protected copyright. Pathology, Academic frequently in large cell B cell lymphomas In a pilot experiment of 44 large cell B cell Medical Centre, Amsterdam and is poorly related to anaplastic lymphomas CD30 expression, as demon- L A Noorduyn morphology. Morphological distinction strated by Ber-H224 on formalin fixed, paraf- Department of between anaplastic and non-anaplastic fin wax embedded tissue, gave many false Pathology, Free tumours is difficult. In contrast to T cell negative results when compared with frozen University Hospital, B sections we decided to use Amsterdam lymphomas, CD30 positive cell lym- (fig 1). Therefore, P C de Bruin phomas do not show a relatively only those large cell lymphomas from which CJLMMeijer favourable clinical course. The results frozen tissue was available. We therefore col- Netherlands Cancer presented here raise serious doubts as to lected 146 cases of large cell lymphoma from Institute whether large cell B cell lymphoma, the files of the Comprehensive Cancer Centre P van Heerde based on the expression of CD30 or Amsterdam (CCCA). Routinely stained Slotervaart Hospital, and Amsterdam anaplastic morphology, can really be slides (haematoxylin eosin, reticulin, M M van de Sandt termed a separate entity. Giemsa, and periodic acid Schiff), and data Department of on immunohistochemistry were also collected Haematology, Free (3 Clin Pathol 1994;47:33-37) from all cases. University Hospital, Staining with Ber-H2 on frozen sections Amsterdam G J Ossenkoppele was performed according to standard proce- as Correspondence to: In 1982 a monoclonal antibody that reacted dures. Tumours were scored positive (+) Dr L A Noorduyn, selectively with Hodgkin and Reed-Stemnberg if at least 50% of the tumour cells were Department of Pathology, Academic Medical Centre, cells was described by Schwab et al.' Ki-i stained clearly and dubious (+ /-) if less Meibergdreef 9, 1105 AZ (CD30) was subsequently shown to react than 50% of the tumour cells were stained or Amsterdam, The Netherlands with a number of large cell non-Hodgkin's if staining was weak. Morphological investiga- Accepted for publication lymphomas. Recently, it has been shown that tion of the tumours was performed with the 18 August 1993. Ki-i detects an antigen that is a member of help of routinely stained slides, without prior 34 Noorduyn, Bruin, Heerde, Sandt, Ossenkoppele, Meijer .... V4, knowledge of the results of Ber-H2 staining. 9-go" .:. Morphologically, the tumours were graded .* according to the updated Kiel classification.4 i .. Tumours were scored as anaplastic if they ... J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994. Downloaded from met the criteria described by Suchi et al and Lennert.526 In short, anaplastic lymphomas 4 were characterised by large or very large cells, 4. * with abundant cytoplasm, with large, often and usually mul- ..... ...... reniform or indented nuclei, w. tiple, medium sized to large nucleoli. The ._: i :. i. tumour often showed an intrasinusoidal '4 growth pattern. ./:O..§. .... w.s., *: °\ ...... ... Of the tumours that were scored as + or * .e:*: .S :> ffiW- A">Z:X:.: '4, if}S%;R:. * u R;iu)+ /-)and from a control group of 25 A1 {:Aj.!. *.*..: *, :& * i # tumours that were scored as -, clinical :' # ..... .: and follow up data were collected from the .. IP e patients' records. This group of 25 patients whose tumours were completely CD30 nega- : *.z .. , g ...- tive was used as a control group for survival analysis. It included three patients with :. ...:: . anaplastic, but immuno- ...., .":o. ....e..:.A morphologically histochemically CD30 negative, tumours. JR-.if>. ... - .: vR* ..^'w bioi.. Statistical analysis of these data was Figure 1 Polymorphic centroblastic B cell lymphoma. Staining with Be? paraffin wax section is negative. Inset: staining with Ber-H2 onfrozen section is I-Ht2ven performed with the help of a BMDP package. Results The numbers of positive tumours for each morphological subtype are shown in the Expression ofCD30 (Ber-H2) in 146 large cell B cell table. In most tumours in the CD30+ cate- lymphomas, according to morphological subtype gory, over 80% of tumour cells were positive, and in the CD30 + / - category generally less CD30 than 20% were positive. Only a few tumours + - Total expressed CD30 in tumour cells close to the B cell lymphomas cutoff point of 50%. Follicular centroblastic 2 5 7 14 Of the B cell lymphomas that were mor- Centrocytoid centroblastic 2 10 29 41 Centroblastic 2 5 22 29 phologically scored as anaplastic (fig 2), 50% Polymorphic centroblastic 9 7 21 37 were positive with CD30, but of the Immunoblastic 2 1 6 9 http://jcp.bmj.com/ Anaplastic 8 2 6 16 immunoblastic and polymorphic centroblastic Total 25 30 91 146 tumours, 22% and 24%, respectively, were + > 50% of the tumour cells positive; + < 50% of the also positive. Even the other groups of large tumour cells positive, or weak staining; - tumour cells cell B cell lymphoma included cases which negative. were positive with CD30, and a considerable percentage of these tumours showed partial or weak staining of the tumour cells. Only 65% of the morphologically non-anaplastic on October 2, 2021 by guest. Protected copyright. tumours were completely negative with CD30. In reviewing the morphology of the tumours, it was often difficult to differentiate anaplastic and non-anaplastic tumours. In particular, the distinction between poly- .S.. : 0, morphic centroblastic lymphomas and X.! t. immunoblastic B cell lymphomas on the one ::: ::. hand, and anaplastic large cell B cell lym- *:::: :.: phomas on the other, was hard to make when the lymph node was completely invaded, and *# ,u.if > >ak therefore, the characteristic intrasinusoidal .:: i:. growth pattern of anaplastic large cell lym- phoma could not be seen. All these types of :*b. .U. ..f e.: f lymphoma were composed of large cells, .Z:z,:2' 'S usually with abundant cytoplasm, and .- :.e t: .: .:.' : anaplastic nuclei were detected in varying !§2 '' amounts in all of them. Therefore, the dis- .: .S.:e,:....w. tinction was made by estimating the propor- tion of anaplastic nuclei, but we felt that ... : placing these tumours in one category or :... '' another was often arbitrary. Of the cases that expressed CD30, 25 4. .'. patients were men, 10 of whom were in ....Figure: S.t,:^:;*t. e |.... r .:....... ::: ae:., .% 's3':.2'....,.... ' :.:.... '° 3..Anaplastic<... : .. ......: nsslt.?.: .X. :e ffly:.:::; .. s::. : large cell lymphoma, B cell type (haematoxylin and eosin). the CD30 + category, with 15 in the Relation ofCD30 expression to survival and morphology in large cell B cell lymphomas 35 Figure 3 Survival curves tumours died of their disease, with a mean ofCD30 +, CD30 +/-, lOOr - CD30 + and CD30 - large cell B 90 It-I --- CD30 +/- survival of 13 months. The other 14 patients cell lymphomas. No .CD30- with CD30- lymphomas were alive with a 80 - significant difference was § mean follow up of 47 months. There was no seen between any ofthe 70 :...'.n = 25 J Clin Pathol: first published as 10.1136/jcp.47.1.33 on 1 January 1994.
Load more

Recommended publications
  • Human Angiogenin Fused to Human CD30 Ligand (Ang-CD30L) Exhibits Specific Cytotoxicity Against CD30-Positive Lymphoma1
    [CANCER RESEARCH 61, 8737–8742, December 15, 2001] Human Angiogenin Fused to Human CD30 Ligand (Ang-CD30L) Exhibits Specific Cytotoxicity against CD30-positive Lymphoma1 Michael Huhn, Stephanie Sasse, Mehmet K. Tur, Ba¨rbel Matthey, Timo Schinko¨the, Susanna M. Rybak, Stefan Barth,2 and Andreas Engert Fraunhofer IME, Department of Pharmaceutical Product Development, 52074 Aachen, Germany [M. K. T., M. H., S. B.]; Laboratory of Immunotherapy, Department I of Internal Medicine, University Hospital Cologne, 50931 Cologne, Germany [S. S., B. M., T. S., A. E.]; Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702 [S. M. R.] ABSTRACT first and then to administer ITs to kill residual H-RS cells. One of the most promising target antigens for immunotherapy of malignant lym- A number of different immunotoxins composed of cell-specific target- phoma such as Hodgkin’s lymphoma or anaplastic large cell lym- ing structures coupled to plant or bacterial toxins have increasingly been phoma is the CD30 receptor. This antigen was originally discovered evaluated for immunotherapy. Because these foreign proteins are highly immunogenic in humans, we have developed a new CD30 ligand-based on cultured H-RS cells using the moab Ki-1 (1). The gene encoding fusion toxin (Ang-CD30L) using the human RNase angiogenin. The com- the CD30 receptor molecule (2) is located on chromosome 1p36. The pletely human fusion gene was inserted into a pET-based expression naturally occurring CD30 ligand has also been identified and cloned plasmid. Transformed Escherichia coli BL21(DE3) were grown under (3).
    [Show full text]
  • Tools for Cell Therapy and Immunoregulation
    RnDSy-lu-2945 Tools for Cell Therapy and Immunoregulation Target Cell TIM-4 SLAM/CD150 BTNL8 PD-L2/B7-DC B7-H1/PD-L1 (Human) Unknown PD-1 B7-1/CD80 TIM-1 SLAM/CD150 Receptor TIM Family SLAM Family Butyrophilins B7/CD28 Families T Cell Multiple Co-Signaling Molecules Co-stimulatory Co-inhibitory Ig Superfamily Regulate T Cell Activation Target Cell T Cell Target Cell T Cell B7-1/CD80 B7-H1/PD-L1 T cell activation requires two signals: 1) recognition of the antigenic peptide/ B7-1/CD80 B7-2/CD86 CTLA-4 major histocompatibility complex (MHC) by the T cell receptor (TCR) and 2) CD28 antigen-independent co-stimulation induced by interactions between B7-2/CD86 B7-H1/PD-L1 B7-1/CD80 co-signaling molecules expressed on target cells, such as antigen-presenting PD-L2/B7-DC PD-1 ICOS cells (APCs), and their T cell-expressed receptors. Engagement of the TCR in B7-H2/ICOS L 2Ig B7-H3 (Mouse) the absence of this second co-stimulatory signal typically results in T cell B7-H1/PD-L1 B7/CD28 Families 4Ig B7-H3 (Human) anergy or apoptosis. In addition, T cell activation can be negatively regulated Unknown Receptors by co-inhibitory molecules present on APCs. Therefore, integration of the 2Ig B7-H3 Unknown B7-H4 (Mouse) Receptors signals transduced by co-stimulatory and co-inhibitory molecules following TCR B7-H5 4Ig B7-H3 engagement directs the outcome and magnitude of a T cell response Unknown Ligand (Human) B7-H5 including the enhancement or suppression of T cell proliferation, B7-H7 Unknown Receptor differentiation, and/or cytokine secretion.
    [Show full text]
  • Autologous T Cells Expressing CD30 Chimeric Antigen Receptors For
    Published OnlineFirst August 31, 2016; DOI: 10.1158/1078-0432.CCR-16-1365 Cancer Therapy: Clinical Clinical Cancer Research Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial Chun-Meng Wang1, Zhi-Qiang Wu2,YaoWang3, Ye-Lei Guo3,Han-RenDai3, Xiao-Hui Wang2, Xiang Li2, Ya-Jing Zhang1,Wen-YingZhang1, Mei-Xia Chen1, Yan Zhang1, Kai-Chao Feng1,YangLiu4,Su-XiaLi4, Qing-Ming Yang1, and Wei-Dong Han3 Abstract Purpose: Relapsed or refractory Hodgkin lymphoma is a chal- tolerated, with grade 3 toxicities occurring only in two of 18 lenge for medical oncologists because of poor overall survival. We patients. Of 18 patients, seven achieved partial remission and six aimed to assess the feasibility, safety, and efficacy of CD30- achieved stable disease. An inconsistent response of lymphoma targeting CAR T cells in patients with progressive relapsed or was observed: lymph nodes presented a better response than refractory Hodgkin lymphoma. extranodal lesions and the response of lung lesions seemed to Experimental Design: Patients with relapsed or refractory be relatively poor. Lymphocyte recovery accompanied by an Hodgkin lymphoma received a conditioning chemotherapy fol- increase of circulating CAR T cells (peaking between 3 and 9 days lowed by the CART-30 cell infusion. The level of CAR transgenes after infusion) is a probable indictor of clinical response. Analysis in peripheral blood and biopsied tumor tissues was measured of biopsied tissues by qPCR and immunohistochemistry revealed periodically according to an assigned protocol by quantitative the trafficking of CAR T cells into the targeted sites and reduction PCR (qPCR).
    [Show full text]
  • Clinical Trials of CAR-T Cells in China Bingshan Liu1,2, Yongping Song2* and Delong Liu2*
    Liu et al. Journal of Hematology & Oncology (2017) 10:166 DOI 10.1186/s13045-017-0535-7 RAPID COMMUNICATION Open Access Clinical trials of CAR-T cells in China Bingshan Liu1,2, Yongping Song2* and Delong Liu2* Abstract Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications. Multi-target CAR-engineered T cells are also entering clinical trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new frontiers in CAR-T cell development. In this study, we analyzed the characteristics of CAR constructs and registered clinical trials of CAR-T cells in China and provided a quick glimpse of the landscape of CAR-T studies in China. Background “third generation chimeric,” and “fourth generation chimeric”; Novel immunotherapeutic agents targeting CTLA-4, country: China. All relevant trials registered at the Clinical- programmed cell death-1 protein receptor (PD-1), and the Trials.gov prior to July 18, 2017, were included in the analysis. ligand PD-L1 are revolutionizing cancer therapy [1–7]. One trial was excluded (NCT03121625) because the target Cancer immunotherapy by re-igniting T cells through antigen was not disclosed. A search of the PubMed blocking PD-1 and PD-L1 is highly potent in a variety of databasewasalsodonetoincludethosetrialsand malignancies [8–12].
    [Show full text]
  • CD134/OX40 Code No
    D125-3 For Research Use Only. Page 1 of 2 Not for use in diagnostic procedures. MONOCLONAL ANTIBODY CD134/OX40 Code No. Clone Subclass Quantity Concentration D125-3 W4-3 Rat IgG2a 100 L 1 mg/mL BACKGROUND: OX40 (CD134/TNFRSF4/ACT35) is SPECIES CROSS REACTIVITY: a 50 kDa of cell surface glycoprotein. OX40, a member of Species Human Mouse Rat the tumor necrosis factor (TNF) superfamily, is expressed primarily on activated CD4+ T cells. OX40 interacts with Cells MT2, HPB-MLT Not Tested Not Tested OX40 ligand antigen (OX40L, also known as CD252/gp34/CD134L) expressed on activated B cells and Reactivity on FCM + antigen presenting cells results in enhanced T cell proliferation and induction of IL-2 production. REFERENCES: OX40/OX40L interaction provides a costimulatory signal, 1) Kawamata, S., et al., J. Biol. Chem. 273, 5808-5814 (1998) resulting in enhanced T cell proliferation and cytokine 2) Latza, U., et al., Europ. J. Immun. 24, 677-683 (1994) production. Then, cell proliferation and immunoglobulin secretion in activated B cells are enhanced. OX40/OX40L system mediates the adhesion of activated or HTLV-I-transformed T cells to vascular endothelial cells. TRAF2 and TRAF5 binding to OX40 led to NF-B activation, and TRAF3 binding appeared to inhibit NF-B activation SOURCE: This antibody was purified from C.B-17 SCID mice ascites fluid using protein A agarose. This hybridoma (clone W4-3) was established by fusion of mouse myeloma cell SP2/0 with WKA/H rat splenocyte immunized with the human OX40 transfectant. Flow cytometric analysis of CD134 expression on HPB-MLT (left) and PM1 FORMULATION: 100 g IgG in 100 L volume of (right).
    [Show full text]
  • Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy
    cells Review Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy Jan A. Rath and Caroline Arber * Department of oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, 1015 Lausanne, Switzerland * Correspondence: [email protected] Received: 18 May 2020; Accepted: 16 June 2020; Published: 18 June 2020 Abstract: T cell receptor (TCR)-based adoptive T cell therapies (ACT) hold great promise for the treatment of cancer, as TCRs can cover a broad range of target antigens. Here we summarize basic, translational and clinical results that provide insight into the challenges and opportunities of TCR-based ACT. We review the characteristics of target antigens and conventional αβ-TCRs, and provide a summary of published clinical trials with TCR-transgenic T cell therapies. We discuss how synthetic biology and innovative engineering strategies are poised to provide solutions for overcoming current limitations, that include functional avidity, MHC restriction, and most importantly, the tumor microenvironment. We also highlight the impact of precision genome editing on the next iteration of TCR-transgenic T cell therapies, and the discovery of novel immune engineering targets. We are convinced that some of these innovations will enable the field to move TCR gene therapy to the next level. Keywords: adoptive T cell therapy; transgenic TCR; engineered T cells; avidity; chimeric receptors; chimeric antigen receptor; cancer immunotherapy; CRISPR; gene editing; tumor microenvironment 1. Introduction Adoptive T cell therapy (ACT) with T cells expressing native or transgenic αβ-T cell receptors (TCRs) is a promising treatment for cancer, as TCRs cover a wide range of potential target antigens [1].
    [Show full text]
  • CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30 And
    Published OnlineFirst August 7, 2018; DOI: 10.1158/2326-6066.CIR-18-0065 Research Article Cancer Immunology Research CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30þ and CD30– Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions Lee K. Hong1, Yuhui Chen2, Christof C. Smith1, Stephanie A. Montgomery3, Benjamin G. Vincent2, Gianpietro Dotti1,2, and Barbara Savoldo2,4 Abstract Tumor antigen heterogeneity limits success of chimeric (NSG) mouse model of metastatic EC. We observed that CD30. þ antigen receptor (CAR) T-cell therapies. Embryonal carcino- CAR T cells, while targeting CD30 EC tumor cells through mas (EC) and mixed testicular germ cell tumors (TGCT) the CAR (i.e., antigen-dependent targeting), also eliminated – containing EC, which are the most aggressive TGCT subtypes, surrounding CD30 EC cells in an antigen-independent man- are useful for dissecting this issue as ECs express the CD30 ner, via a cell–cell contact-dependent Fas/FasL interaction. In – þ – antigen but also contain CD30 /dim cells. We found that CD30- addition, ectopic Fas (CD95) expression in CD30 Fas EC was redirected CAR T cells (CD30.CAR T cells) exhibit antitumor sufficient to improve CD30.CAR T-cell antitumor activity. activity in vitro against the human EC cell lines Tera-1, Tera-2, Overall, these data suggest that CD30.CAR T cells might be and NCCIT and putative EC stem cells identified by Hoechst useful as an immunotherapy for ECs. Additionally, Fas/FasL dye staining. Cytolytic activity of CD30.CAR T cells was com- interaction between tumor cells and CAR T cells can be plemented by their sustained proliferation and proinflamma- exploited to reduce tumor escape due to heterogeneous antigen tory cytokine production.
    [Show full text]
  • CD30 Induction of Human Immunodeficiency Virus Gene Transcription Is Mediated by TRAF2
    Proc. Natl. Acad. Sci. USA Vol. 94, pp. 1390–1395, February 1997 Immunology CD30 induction of human immunodeficiency virus gene transcription is mediated by TRAF2 ERDYNI N. TSITSIKOV,DOWAIN A. WRIGHT, AND RAIF S. GEHA* Division of Immunology, Children’s Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115 Communicated by Louis Kunkel, Harvard Medical School, Boston, MA, December 17, 1996 (received for review September 4, 1996) ABSTRACT CD30 is a member of the tumor necrosis TRAF3, TRAF4 (CART1), and TRAF5 (17–21). TRAF-1 factor receptor (TNFR) superfamily expressed on activated T and TRAF-2 were found to associate with the intracellular and B lymphocytes and natural killer cells. Ligation of CD30 domain of TNFR2 (16). However, TRAF1 is indirectly asso- was previously shown to induce NF-kB activation and HIV ciated with TNFR2 via dimerization with TRAF2, whereas expression in chronically infected T lymphocytes. In this TRAF2 and TRAF3 bind directly to CD40 (18–20, 22). study, we report that two members of the TNFR-associated TRAF3 is also associated with the lymphotoxin-b receptor and factor (TRAF) family of proteins, TRAF1 and TRAF2, inde- TNFR2 (20). Recently, it was shown that TRAF5 binds to the pendently bind to the intracellular domain of CD30 (CD30IC). lymphotoxin-b receptor (21). TRAF4 was cloned from a breast Transient overexpression of TRAF2, but not TRAF1, induced carcinoma cell line and is the only TRAF that has been NF-kB activation and HIV-1-long terminal repeat-driven localized to the nucleus and may not be associated with a transcription in the T cell line, KT3.
    [Show full text]
  • Molecular Biology of Hodgkin Lymphoma
    Leukemia (2021) 35:968–981 https://doi.org/10.1038/s41375-021-01204-6 REVIEW ARTICLE Lymphoma Molecular biology of Hodgkin lymphoma 1 1 Marc A. Weniger ● Ralf Küppers Received: 17 November 2020 / Revised: 1 February 2021 / Accepted: 18 February 2021 / Published online: 8 March 2021 © The Author(s) 2021. This article is published with open access Abstract Classical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells 1234567890();,: 1234567890();,: from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV+ cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion.
    [Show full text]
  • B-Cell Maturation Antigen Expression Across Hematologic Cancers: a Systematic Literature Review
    Dogan et al. Blood Cancer Journal (2020) 10:73 https://doi.org/10.1038/s41408-020-0337-y Blood Cancer Journal REVIEW ARTICLE Open Access B-cell maturation antigen expression across hematologic cancers: a systematic literature review Ahmet Dogan 1, David Siegel2,NguyetTran3,AlanFu3, Jessica Fowler3, Rajesh Belani3 and Ola Landgren 1 Abstract B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma.
    [Show full text]
  • Download of These Slides, Please Direct Your Browser to the Following Web Address
    Clinical Roundtable Monograph Clinical Advances in Hematology & Oncology April 2014 CD30 in Lymphoma: Its Role in Biology, Diagnostic Testing, and Targeted Therapy Discussants Eduardo M. Sotomayor, MD Susan and John Sykes Endowed Chair in Hematologic Malignancies Moffitt Cancer Center Scientific Director, DeBartolo Family Personalized Medicine Institute Professor, Department of Oncologic Sciences and Pathology & Cell Biology University of South Florida College of Medicine Tampa, Florida Ken H. Young, MD, PhD Associate Professor The University of Texas MD Anderson Cancer Center Department of Hematopathology Houston, Texas Anas Younes, MD Chief of Lymphoma Service Memorial Sloan Kettering Cancer Center New York, New York Abstract: CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E.
    [Show full text]
  • Human Alloimmune Responses Proliferating T Lymphocyte
    CD30 Expression Identifies the Predominant Proliferating T Lymphocyte Population in Human Alloimmune Responses This information is current as Keith W. Chan, Corwyn D. Hopke, Sheri M. Krams and of October 5, 2021. Olivia M. Martinez J Immunol 2002; 169:1784-1791; ; doi: 10.4049/jimmunol.169.4.1784 http://www.jimmunol.org/content/169/4/1784 Downloaded from References This article cites 39 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/169/4/1784.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 5, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CD30 Expression Identifies the Predominant Proliferating T Lymphocyte Population in Human Alloimmune Responses1 Keith W. Chan,* Corwyn D. Hopke,† Sheri M. Krams,*† and Olivia M. Martinez2*† CD30 is an inducible member of the TNFR superfamily that is expressed on activated T and B cells and some lymphoid malig- nancies.
    [Show full text]