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Cancers
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Novel Markers in Lymphoma
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Novel Markers in Lymphoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 14723

Special Issue Editor

Dr. Ayse U. Akarca

E-Mail Website
Guest Editor
Department of Histopathology, University College London Hospital, London, UK
Interests: haematological malignancies; solid tumours; tumour microenvironment; immunotherapy; biomarkers; immunohistochemistry; imaging; technological development

Special Issue Information

Dear Colleagues,

Lymphomas are a heterogeneous group of haematological malignancies derived from lymphocytes and have interrelating diagnostic characteristics. Unlike other malignancies, lymphomas do not provide a clear prognostic impact as patients over time develop rapid progression to more aggressive diseases. Advancements in efficient detection platforms such as multiplex immunohistochemistry as well as other techniques have allowed for the development of a number of novel biomarkers at genetic, epigenetic, and protein levels to be discovered. Biomarkers provide an opportunity for new clinical and pathological insights into the essential mechanisms of lymphomagenesis. Additionally, these biomarkers have a key role in improving diagnosis, staging and sub-classification, and prognostic assessment. In this Special Issue of Cancers, experts will review current diagnostic and prognostic approaches in the field of lymphoma.

Dr. Ayse U. Akarca
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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • B-cell lymphoma
  • T-cell lymphoma
  • diagnosis
  • prognosis
  • biomarker
  • microenvironment
  • targeted therapy
  • relapse
  • immune response

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Published Papers (5 papers)

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Research

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13 pages, 1236 KiB  
Article
Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia
by Anna Guarini, Giulia Radice, Nadia Peragine, Chiara Buracchi, Maria Stefania De Propris, Alice Di Rocco, Arianna Di Rocco, Sabina Chiaretti, Alex Moretti, Sara Napolitano, Maurizio Martelli, Adriana Balduzzi, Giuseppe Gaipa, Andrea Biondi and Robin Foà
Cancers 2023, 15(9), 2411; https://doi.org/10.3390/cancers15092411 - 22 Apr 2023
Cited by 3 | Viewed by 2010
Abstract
Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in [...] Read more.
Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients’ immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults. Full article
(This article belongs to the Special Issue Novel Markers in Lymphoma)
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24 pages, 6851 KiB  
Article
Tissue-Specific microRNA Expression Profiling to Derive Novel Biomarkers for the Diagnosis and Subtyping of Small B-Cell Lymphomas
by Susan Swee-Shan Hue, Yu Jin, He Cheng, Muhammad Sufyan Bin Masroni, Lloyd Wei Tat Tang, Yong Howe Ho, Diana Bee-Lan Ong, Sai Mun Leong and Soo Yong Tan
Cancers 2023, 15(2), 453; https://doi.org/10.3390/cancers15020453 - 10 Jan 2023
Cited by 4 | Viewed by 3023
Abstract
Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish [...] Read more.
Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions. Full article
(This article belongs to the Special Issue Novel Markers in Lymphoma)
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16 pages, 1293 KiB  
Article
Impaired Global Longitudinal Strain Is Associated with Cardiovascular Events in Hodgkin Lymphoma Survivors
by Elissa A. S. Polomski, Julius C. Heemelaar, Augustinus D. G. Krol, Marloes Louwerens, Saskia L. M. A. Beeres, Eduard R. Holman, J. Wouter Jukema, Martin J. Schalij and M. Louisa Antoni
Cancers 2022, 14(9), 2329; https://doi.org/10.3390/cancers14092329 - 8 May 2022
Viewed by 2652
Abstract
Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect [...] Read more.
Background: Treatment with thoracic irradiation for classic Hodgkin lymphoma (CHL) leads to improved survival but also increases the risk of cardiovascular events. Left ventricular (LV) dysfunction is usually assessed by echocardiographic left ventricular ejection fraction (LVEF), whereas global longitudinal strain (GLS) can detect early subclinical LV dysfunction. The purpose of this study was to evaluate if conventional echocardiographic parameters and GLS are associated with cardiovascular events during long-term follow-up. Methods: 161 consecutive CHL patients treated with radiotherapy who underwent echocardiography > 10 years after diagnosis were assessed for eligibility. Multivariable cause-specific Cox regression was performed for a composite outcome of cardiac death and cardiovascular events and the competing outcome of noncardiac death. Results: 129 patients (61.2% female, N = 79) with a mean age of 46.3 ± 11.0 years at index visit were eligible for analysis. GLS was impaired in 51 patients (39.5%) and 10.9% had a LVEF of< 50%. The median E/e’ was 9.2 [7.2;12.7]. Adjusted for confounders, GLS > −16% showed a significant association with a near four-fold risk of the composite endpoint (HR = 3.95, 95% CI: 1.83–8.52, p < 0.001). LVEF < 50% (HR = 2.99, p = 0.016) and E/e’ (HR = 1.16, p < 0.001) also showed a significant relationship with the outcome. None of the aforementioned parameters were associated with the competing outcome. Conclusions: This study shows that LV dysfunction including impaired GLS in CHL survivors is associated with cardiovascular events and cardiac death. Full article
(This article belongs to the Special Issue Novel Markers in Lymphoma)
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13 pages, 1946 KiB  
Article
Classic Hodgkin Lymphoma Refractory for ABVD Treatment Is Characterized by Pathologically Activated Signal Transduction Pathways as Revealed by Proteomic Profiling
by Bent Honoré, Maja Dam Andersen, Diani Wilken, Peter Kamper, Francesco d’Amore, Stephen Hamilton-Dutoit and Maja Ludvigsen
Cancers 2022, 14(1), 247; https://doi.org/10.3390/cancers14010247 - 4 Jan 2022
Cited by 3 | Viewed by 3008
Abstract
In classic Hodgkin lymphoma (cHL), the tumour microenvironment (TME) is of major pathological relevance. The paucity of neoplastic cells makes it important to study the entire TME when searching for prognostic biomarkers. Cure rates in cHL have improved markedly over the last several [...] Read more.
In classic Hodgkin lymphoma (cHL), the tumour microenvironment (TME) is of major pathological relevance. The paucity of neoplastic cells makes it important to study the entire TME when searching for prognostic biomarkers. Cure rates in cHL have improved markedly over the last several decades, but patients with primary refractory disease still show inferior survival. We performed a proteomic comparison of pretreatment tumour tissue from ABVD treatment-refractory versus ABVD treatment-sensitive cHL patients, in order to identify biological differences correlating with treatment outcome. Formalin-fixed paraffin-embedded tumour tissues from 36 patients with cHL, 15 with treatment-refractory disease, and 21 with treatment-sensitive disease, were processed for proteomic investigation. Label-free quantification nano liquid chromatography tandem mass spectrometry was performed on the tissues. A total of 3920 proteins were detected and quantified between the refractory and sensitive groups. This comparison revealed several subtle but significant differences in protein expression which could identify subcluster characteristics of the refractory group. Bioinformatic analysis of the biological differences indicated that a number of pathologically activated signal transduction pathways are disturbed in ABVD treatment-refractory cHL. Full article
(This article belongs to the Special Issue Novel Markers in Lymphoma)
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Review

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17 pages, 2281 KiB  
Review
Genetic Alterations in Adult T-Cell Leukemia/Lymphoma: Novel Discoveries with Clinical and Biological Significance
by Shugo Sakihama and Kennosuke Karube
Cancers 2022, 14(10), 2394; https://doi.org/10.3390/cancers14102394 - 12 May 2022
Cited by 3 | Viewed by 2762
Abstract
Adult T-cell leukemia/lymphoma (ATLL) is a refractory T-cell neoplasm that develops in human T-cell leukemia virus type-I (HTLV-1) carriers. Large-scale comprehensive genomic analyses have uncovered the landscape of genomic alterations of ATLL and have identified several altered genes related to prognosis. The genetic [...] Read more.
Adult T-cell leukemia/lymphoma (ATLL) is a refractory T-cell neoplasm that develops in human T-cell leukemia virus type-I (HTLV-1) carriers. Large-scale comprehensive genomic analyses have uncovered the landscape of genomic alterations of ATLL and have identified several altered genes related to prognosis. The genetic alterations in ATLL are extremely enriched in the T-cell receptor/nuclear factor-κB pathway, suggesting a pivotal role of deregulation in this pathway in the transformation of HTLV-1-infected cells. Recent studies have revealed the process of transformation of HTLV-1-infected cells by analyzing longitudinal samples from HTLV-1 carriers and patients with overt ATLL, an endeavor that might enable earlier ATLL diagnosis. The latest whole-genome sequencing study discovered 11 novel alterations, including CIC long isoform, which had been overlooked in previous studies employing exome sequencing. Our study group performed the targeted sequencing of ATLL in Okinawa, the southernmost island in Japan and an endemic area of HTLV-1, where the comprehensive genetic alterations had never been analyzed. We found associations of genetic alterations with HTLV-1 strains phylogenetically classified based on the tax gene, an etiological virus factor in ATLL. This review summarizes the genetic alterations in ATLL, with a focus on their clinical significance, geographical heterogeneity, and association with HTLV-1 strains. Full article
(This article belongs to the Special Issue Novel Markers in Lymphoma)
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