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Biomedicines
Special Issues
Translational Discoveries in T-cell Lymphomas
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Translational Discoveries in T-cell Lymphomas

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 9492

Special Issue Editors

Dr. Danilo Fiore

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Tommaso De Amicis 95, Laboratori IEOS, CNR, Scala C, III piano, 80131 Naples, Italy
Interests: T-Cell Lymphoma; Patient-Derived models; JAK-STAT3; Lymphoma microenvironment; Lymphoma Biomarkers and Classifiers; T-Cell Lymphoma immunotherapy
Dr. Luca Vincenzo Cappelli

E-Mail Website
Co-Guest Editor
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
Interests: drug discovery; chronic lymphocytic leukemia (cll); Peripheral T cell lymphomas (PTCLs); oncology

Special Issue Information

Dear Colleagues,

Despite the introduction of successful novel therapeutic approaches in the treatment of human lymphomas, the survival of patients with T-cell lymphomas (TCL) is dismal. As of today, remarkable advancements have been impaired by TCL rarity and the limited knowledge of pathogenetic mechanisms, together with a lack of reliable pre-clinical models. Recent efforts have led to dramatic improvements in TCL functional and genetic stratification, leading to a fast-evolving scenario. In this new perspective, we predict that the integration of TCL phenotypic and molecular features will foster translational discoveries to be tested in new informative pre-clinical models, ultimately refining diagnosis and improving the clinical outcome of patients.

This Special Issue aims to collect research articles and reviews from researchers investigating different aspects of TCL tumorigenesis, with a focus on translational discoveries accounting for new targeted agents, immunotherapies and chimeric antigen receptor (CAR)-adoptive strategies (CAR-T/CAR-NK cells).

Dr. Danilo Fiore
Guest Editor
Dr. Luca Vincenzo Cappelli
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • T-Cell Lymphoma
  • Patient-Derived models
  • Lymphoma microenvironment
  • Lymphoma Biomarkers and Classifiers
  • T-Cell Lymphoma immunotherapy
  • CAR-T cells

Published Papers (3 papers)

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Research

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16 pages, 3394 KiB  
Article
Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
by Franziska Lea Schümann, Elisabeth Groß, Marcus Bauer, Christian Rohde, Sarah Sandmann, Denis Terziev, Lutz P. Müller, Guido Posern, Andreas Wienke, Falko Fend, Martin-Leo Hansmann, Wolfram Klapper, Andreas Rosenwald, Harald Stein, Martin Dugas, Carsten Müller-Tidow, Claudia Wickenhauser, Mascha Binder and Thomas Weber
Biomedicines 2021, 9(12), 1842; https://doi.org/10.3390/biomedicines9121842 - 5 Dec 2021
Cited by 8 | Viewed by 3381
Abstract
T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay [...] Read more.
T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients. Full article
(This article belongs to the Special Issue Translational Discoveries in T-cell Lymphomas)
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Review

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14 pages, 913 KiB  
Review
The Role of NKL Homeobox Genes in T-Cell Malignancies
by Stefan Nagel
Biomedicines 2021, 9(11), 1676; https://doi.org/10.3390/biomedicines9111676 - 12 Nov 2021
Cited by 1 | Viewed by 1623
Abstract
Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in [...] Read more.
Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in classes and subclasses, including NKL homeobox genes. In accordance with their normal functions, deregulated homeobox genes contribute to carcinogenesis along with hematopoietic malignancies. We have recently described the physiological expression of eleven NKL homeobox genes in the course of hematopoiesis and termed this gene expression pattern NKL-code. Due to the developmental impact of NKL homeobox genes these data suggest a key role for their activity in the normal regulation of hematopoietic cell differentiation including T-cells. On the other hand, aberrant overexpression of NKL-code members or ectopical activation of non-code members has been frequently reported in lymphoid and myeloid leukemia/lymphoma, demonstrating their oncogenic impact in the hematopoietic compartment. Here, we provide an overview of the NKL-code in normal hematopoiesis and discuss the oncogenic role of deregulated NKL homeobox genes in T-cell malignancies. Full article
(This article belongs to the Special Issue Translational Discoveries in T-cell Lymphomas)
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Other

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13 pages, 39863 KiB  
Case Report
Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma
by Tina Petrogiannis-Haliotis, Kevin Pehr, David Roberge, Ryan N. Rys, Yury Monczak, Gizelle Popradi, Lissa Ajjamada, Naciba Benlimame, Christiane Querfeld, Nathalie Johnson and Hans Knecht
Biomedicines 2023, 11(2), 634; https://doi.org/10.3390/biomedicines11020634 - 20 Feb 2023
Cited by 1 | Viewed by 3713
Abstract
We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the [...] Read more.
We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/− PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1−, CD4+/PD1+, CD8+/PD1− and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL. Full article
(This article belongs to the Special Issue Translational Discoveries in T-cell Lymphomas)
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