Subtype Of Lymphoma Research Articles

Intravascular Large B-Cell Lymphoma With Exclusively Cutaneous Involvement, Colonizing Pre-Existing Hemangiomas: A Rare Case With Aberrant HMB45 Expression.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. It is characterized by the presence of neoplastic lymphoid cells within blood vessels. We report a rare case of IVLBCL with exclusively cutaneous involvement colonization of hemangiomas. A 55-year-old man with a history of cutaneous angioma consulted dermatology because of the growth of some of the hemangiomas in recent months. Histologic examination revealed a dermal proliferation of small- and medium-sized vessels with lumina occupied by large pleomorphic cells with B immunophenotype and aberrant expression of HMB-45. Biopsy of a pre-existing hemangioma may be useful in the diagnosis of suspected cutaneous IVLBCL. The cutaneous variant has a better prognosis. It is also important to note that unexpected protein expression or loss of expression in malignant tumors may be a risk factor for misdiagnosis.

Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment.

The activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell-like subtype (GCB-DLBCL). Currently, targeting the tumor microenvironment (TME) is the most promising approach to cure DLBCL with profound molecular heterogeneity; however, the factors affecting the tumor-promoting TME of ABC-DLBCL remain elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABC-DLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response, but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME, enhancing angiogenesis and the expression of cytokine IL-6 and IL-10, as well as decreasing T-cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in co-ordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumor-promoting effects of IL-16, providing new insights into treatment strategy in ABC-DLBCL.

Real-World Data on Lymphoma in Adolescents and Young Adults (AYA)-Report From the Lymphoma and Related Diseases Registry (LaRDR).

Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15-39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options. We performed a retrospective review of patients aged 18-60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18-39 years) and older adults (OAs) (aged 40-60). AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs. The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40-60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes. The authors have confirmed clinical trial registration is not needed for this submission.

Multiple Primary Cutaneous Anaplastic Large Cell Lymphoma: A Case Report

Introduction: Anaplastic large cell lymphomas (ALCL) are a subtype of non-Hodgkin lymphoma categorized into systemic and cutaneous (cALCL) subtypes. cALCL are frequently characterized by their lack of ALK receptor expression, which differentiates them from their systemic counterparts. cALCLs present as solitary or grouped skin lesions. Due to their rarity, cALCLs are frequently misdiagnosed as other skin conditions. Case presentation: We report the case of a female with a 30-year history of expanding skin lesions on the upper and lower limbs, abdomen, and back. During her initial presentation, the lesions were thought to be due to an arthropod bite. However, lesion biopsy revealed ALK-negative cALCL and methicillin-resistant Staphylococcus aureus. A full workup excluded systemic ALCL and, therefore, confirmed the diagnosis of primary cALCL. The patient was placed on methotrexate to treat the lesions and sulfamethoxazole/trimethoprim to treat the infection. Conclusion: Our case highlights the need to consider cALCL in the differential diagnosis of patients with persistent skin lesions.

Frontline treatment of follicular lymphoma: What will it take to change current practice?

Follicular lymphoma is the most common subtype of indolent lymphoma. Despite multiple trials over the past decade showing improved progression-free survival with new first-line therapeutic strategies -such as anti-CD20 maintenance therapy and new glycoengineered anti-CD20 antibodies- no standardized approach has been widely adopted in routine clinical practice. Several factors may explain this, including the increased incidence of infectious adverse events associated with these therapies, particularly during the COVID-19 pandemic, and the lack of overall survival benefit despite long-term follow-up. A general consensus has emerged acknowledging the high prognostic variability of follicular lymphoma, which complicates the adoption of a one-size-fits-all first-line treatment strategy. A plethora of prognostic scores (FLIPI, FLIPI2, PRIMA-PI, m7-FLIPI, FLEX, 23-gene score, etc) has been proposed but none can reliably identify the ~20% of patients that will die within 10 years of first-line immunochemotherpay and for whom a critical medical need remains despite recent therapeutic improvements. Consequently, current prognostic models mainly serve as tools to cross-compare and stratify clinical trials. In this review, we highlight current and future strategies aimed at reshaping frontline treatment paradigms to improve outcomes, including tailored approaches based on risk- or response-adapted designs, development of new predictive -rather than prognostic- tools, approaches to reduce adverse events to enhance health-related quality of life, and the potential use of T-cell-engaging therapies to improve survival in the highest risk patients.

Diffuse Large B-Cell Lymphoma with Plasmablastic Differentiation: Case Report

Introduction: Plasmablastic lymphoma is a subtype of diffuse large B-cell lymphoma. It is more frequent in immunosuppressed patients, with the oral cavity being the most common site of involvement, with less frequency in other extranodal regions such as paranasal sinuses, orbit, skin, bone and soft tissues. It is aggressive and has a poor prognosis, with an average survival of 1 year [1]. Clinical Case: We present he clinical case of a 69-year-old male patient, derived from neurosurgery due to a tumor in the frontal region of two weeks' evolution, nasal ventilatory insufficiency of the left nostril of 2 years' evolution, for 2 months he presented recurrent epistaxis. On physical examination a tumor in the frontal region was evident. CERS plus bicoronal craniectomy, resection of the rhinosinusal tumor was performed. Discussion: Plasmablastic lymphoma is a subtype of diffuse large B-cell lymphoma. It is more frequent in immunosuppressed patients, the oral cavity being the most common site of involvement, less frequently in other extranodal regions as in the case of the patient of rhinosinusal origin [5]. Conclusion: It is a diagnostic challenge, both its clinical and histological characteristics are ambiguous, which reduces the capacity for an accurate and rapid diagnosis, it requires intensive treatment with chemotherapy, however, it has a poor prognosis [7].

Dynamic contrast enhanced MRI in nodal lymphoma: correlation of quantitative MR perfusion parameters with lymphoma subtype, Lugano stage and Ki-67 index.

Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma. To study the correlation of quantitative DCE-MRI parameters of Ktrans, Kep and Ve with subtype, Lugano stage at diagnosis and Ki-67 proliferation index (PI) in nodal lymphoma. 33 patients of age > 12 years with newly diagnosed nodal lymphoma underwent DCE-MRI. Ktrans, Kep and Ve were generated from extended Tofts model and correlated with lymphoma subtype, Lugano staging and Ki-67 PI. Mean Ktrans and Kep values were significantly higher in non-Hodgkin's lymphoma (NHL) than in Hodgkin's lymphoma (HL). Considering Ki-67 PI value of > 45% as aggressive lymphoma, the mean Ktrans (659.37 x 10-3min-1 versus 288.00 x 10-3min-1, p < 0.001) and Kep (1256.63 x 10-3min-1 versus 689.82 x 10-3min-1, p = 0.004) values in aggressive lymphomas were significantly higher compared to non-aggressive lymphomas. ROC curve analysis revealed a threshold Ktrans value of ≥ 359 x 10-3min-1 and Kep value of ≥ 853 x10-3 min-1 for diagnosing aggressive lymphomas with a sensitivity of 95%, 90%, specificity of 100%,82% and diagnostic accuracy of 91.7%,86.7% respectively. There was no significant difference in DCE-MRI parameters of various Lugano stage subgroups. DCE-MRI parameters have the potential to non-invasively predict the subtype, aggression and Ki-67 PI in nodal lymphoma. The knowledge that Ktrans is higher in aggressive lymphomas is novel. It adds to previous literature regarding MR perfusion in various neoplasms.

A Hiding Lymphoma: Angioimmunoblastic T Cell Lymphoma — A Case Report

Angioimmunoblastic T-cell lymphoma (AITL) is now a well-established subtype of mature peripheral T-cell lymphoma (PTCL). Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. AITL afflicts advanced-age individuals with a median age of diagnosis of 65 years of age without a notable gender predisposition. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease. Here we report a case of angioimmunoblastic T cell lymphoma which was diagnosed using endoscopic ultrasound guided fine needle biopsy. Our patient’s lab workup was unremarkable and inconclusive, but the correct diagnosis was established using endoscopic ultrasound guided fine needle biopsy. Chemotherapy started after diagnosis and his condition improved.

Sequential transcriptome profiling: comparative analysis of normal and canine lymphoma preceding detailed T-cell and B-cell subtype comparison.

As the lifespan of companion animals extends, the incidence of tumor also increases. Among these tumors, lymphoma is reported as the most prevalent hematopoietic tumor with a 80-90% prevalence rate. Ongoing research spans multiple domains, aiming to uncover novel therapeutic targets, including small molecular weight inhibitors, antibody treatments, and subtype-specific selective agents. Transcriptional profiling was performed on canine lymphoma samples to identify genes and functional pathways associated with pathogenesis, treatment response, and prognosis. Additionally, genes with potential relevance to the clinical characteristics of T-cell lymphoma (TCL), which is characterized by a low treatment response and poor prognosis, were identified through a comparative analysis of different lymphoma subtypes. Within the canine lymphoma group, HERC5 showed consistent upregulation, a gene similarly implicated in human acute myeloid leukemia but previously no reports exist. Additionally, noteworthy genes, including IKZF2, CCL4, SAA1, and CD40, exhibited differential expression in the TCL group compared to the B-cell lymphoma (BCL) group. The upregulation of HERC5 may impact on canine lymphoma pathogenicity. Furthermore, the upregulation of IKZF2, CCL4, and SAA1, along with the downregulation of CD40, may contribute to adverse clinical characteristics of TCL in dogs.

Definitions and use of tumour bulk in phase 3 lymphoma trials: a comprehensive literature review.

Tumour 'bulk' has historically been considered an important prognostic marker and clinical tool to guide treatment in patients with lymphoma. However, its use and definitions in trial designs varies significantly and it is unclear how this has influenced the relevance of bulk in contemporary practice. This comprehensive literature review evaluated the definitions, applications and prognostic impact of bulk in phase 3 randomised trials in four major lymphoma subtypes. Overall, 87 studies were identified across follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma (HL) with a wide range of bulk thresholds employed (5cm, 6cm, 7cm, 7.5cm, 10cm and >1/3 mediastinal mass ratio (MMR)). The most common threshold was: FL; 7cm (58%), DLBCL; 7.5cm and 10cm (44% each), PTCL; 7.5cm (66%) and HL; 1/3 MMR (91%). Bulk threshold was used by trials to determine eligibility (66%), stratification (24%), as a prognostic risk factor (37%) and decision tool for risk-adapted treatment e.g. radiotherapy (29%), however bulk definitions used for these varied both between, and within, lymphoma subtypes, and even within single trials in 25%. Thirty-two studies incorporated bulk in prognostic analyses with only five showing significance for differential survival outcomes. Our analysis demonstrates high inconsistency in thresholds defining tumour bulk and use of bulk in phase 3 lymphoma trials across eligibility, stratification, therapeutic risk-adaptation plus prognostication. This highlights an urgent need for international consensus on definitions of bulk within trials to improve its prognostic and predictive value and refine its application in clinical practice.

Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation.

Refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a major therapeutic challenge due to its resistance to standard treatments. Engineered T-cells, especially Chimeric Antigen Receptor (CAR) T-cells, have shown promise in overcoming drug resistance. This study investigates the effectiveness of WEE1-engineered T-cells in targeting and eliminating refractory DLBCL in vitro. CAR T-cells were created by transducing a 5th-generation CAR construct designed to recognize WEE1, a surface antigen commonly found on refractory DLBCL cells. The cytotoxic effect of engineered T-cells was tested against Rituximab-resistant DLBCL cells (RR-NU-DUL-1). Apoptosis and cell cycle were evaluated using flow cytometry. Quantitative Real-time PCR (RT-PCR) was used to measure the expression of WEE1, BCL2, and CDK2. The results showed a significant increase in target cell lysis, apoptosis, and necrosis, a significant reduction in the percentage of cells in the G2M phase of the cell cycle, as well as a decrease in gene expression level, indicating strong anti-tumor activity. These findings suggest that CAR T-cell therapy holds great promise for treating refractory DLBCL, offering a potential path for clinical application. This in vitro evaluation highlights the potential of WEE1-engineered T-cells as a targeted treatment strategy for refractory DLBCL, emphasizing their clinical applicability and ability to overcome resistance mechanisms in this aggressive lymphoma subtype.

Advances in the Classification of Aggressive B-cell Lymphomas.

Aggressive B-cell lymphomas are a biologically and clinically very heterogeneous group of tumors that may be related to different stages of B-cell differentiation development. This review aims to summarize recent advances in the understanding of these tumors with a focus on the practical approach to the diagnosis of these entities. We analyze the defining characteristics of the different subtypes of aggressive B-cell lymphomas, including nodal and extranodal diffuse large B-cell lymphoma, virus-associated lymphomas, terminally differentiated B-cell lymphomas, high-grade B-cell lymphomas, and Burkitt lymphoma. This review particularly explores the integration of morphologic, immunophenotypic, and genetic data that refine diagnostic accuracy and prognostic stratification, underscoring the necessity for a standardized approach in clinical practice. By synthesizing current knowledge, this review aims to enhance the understanding of aggressive B-cell lymphomas within the context of the evolving classification system, paving the way for future research and clinical advancements.

Clinical characteristics of lymphoma patients presenting with fever of unknown origin misdiagnosed with connective tissue diseases.

Recognizing and diagnosing lymphoma in patients with fever of unknown origin (FUO) can be challenging, and misdiagnosis is not uncommon. To improve understanding of the clinical characteristics of lymphoma patients presenting with FUO who were misdiagnosed with autoimmune diseases. A retrospective, observational study of 140 consecutive patients with FUO and lymphoma presenting to a tertiary center between January 2017 and December 2023. Patients were divided into those who were correctly diagnosed and those misdiagnosed as connective tissue diseases (CTD) and the clinical features compared. Of 140 lymphoma patients with FUO, 21 patients (15.0%) were misdiagnosed as CTD. The median time between symptom onset and diagnosis was significantly longer in the misdiagnosed group than in the non-misdiagnosed group (11.0 (IQR 6.0, 22.5) months vs. 4.0 (2.5, 9.0) months; p = 0.001). The misdiagnosed group had significantly less lymph node and bone marrow involvement and more skin rashes than the non-misdiagnosed group (47.6% vs. 70.6%, p = 0.039; 23.8% vs. 47.9%, p = 0.040; 47.6% vs. 25.2%, p = 0.036), as well as significantly lower ESR (p = 0.026) and hsCRP (p = 0.049). The misdiagnosed group had higher frequency of ANA/ANCA (57.1% vs. 27.7%; p = 0.008) and anti-phospholipid antibody (42.9% vs. 6.1%; p = 0.008) positivity. The distribution of lymphoma subtypes was different between groups (p = 0.058). Lymphoma patients with an atypical presentation and FUO suggesting inflammatory systemic disease are easily misdiagnosed. Autoantibody positivity is not rare in lymphoma patients with an atypical presentation and FUO, so close follow-up and repeated histopathological examination may be helpful to establishing a correct diagnosis.

GneSeqCOO: a novel method for classifying diffuse large B-cell lymphoma cell of origin based on bulk tumor RNA sequencing profiles

The cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations. This study introduces gneSeqCOO, an algorithm using bulk RNA Sequencing (RNASeq) profiles of individual tumor biopsies for COO classification based on a fixed reference. This method produced consistent per-sample results and was robust to variation in RNA quality and sequencing bias. Validation in >1000 DLBCL samples showed high concordance with the NanoString LST assay, even in cohorts containing only one COO subtype. gneSeqCOO presents a robust and versatile alternative to existing assays, potentially reducing the need for additional samples where RNASeq was already generated. The package is available at https://github.com/Genentech/gneSeqCOO.

Regulation and therapy: the role of ferroptosis in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of B-cell non-Hodgkin's lymphoma (NHL), up to 30%-40% of patients will relapse and 10%-15% of patients have primary refractory disease, so exploring new treatment options is necessary. Ferroptosis is a non-apoptotic cell death mode discovered in recent years. Its occurrence pathway plays an essential impact on the therapeutic effect of tumors. Numerous studies have shown that modulating critical factors in the ferroptosis pathway can influence the growth of tumor cells in hematological malignancies including DLBCL. This review highlights recent advances in ferroptosis-related genes (FRGs), including STAT3, Nrf2, and ZEB1, and focuses on the clinical potential of ferroptosis inducers such as IKE, α-KG, DMF, and APR-246, which are currently being explored in clinical studies for their therapeutic effects in DLBCL. Correlational studies provide a novel idea for the research and treatment of ferroptosis in DLBCL and other hematological malignancies and lay a solid foundation for future studies.

Primary Cutaneous CD8-positive Aggressive Epidermotropic Cytotoxic T-cell Lymphoma Complicated by Paraneoplastic Encephalitis

Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) is a rare subtype of cutaneous T-cell lymphoma with a poor prognosis. We herein report a case of PCAE-CTL accompanied by anti-Ma2 antibody-positive paraneoplastic encephalitis. A 33-year-old woman with erythema and disturbance of consciousness was diagnosed with PCAE-CTL by a skin biopsy. Head magnetic resonance imaging revealed bilateral medial temporal lobe hyperintensity, and anti-Ma2 antibody in the cerebrospinal fluid was positive. She was diagnosed with concurrent anti-Ma2 antibody-positive paraneoplastic encephalitis. In cases of lymphoma with brain lesions, invasion of the central nervous system by lymphoma and paraneoplastic encephalitis should be considered.

MicroRNA Profile of High-Grade B-Cell Lymphoma with 11q Aberration.

High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a rare germi-nal centre lymphoma characterised by a typical gain/loss pattern on chromo-some 11q but without MYC translocation. It shares some features with Burkitt lymphoma (BL), HGBCLs and germinal centre-derived diffuse large B-cell lym-phoma, not otherwise specified (GCB-DLBCL-NOS). Since microRNA expression in HGBCL-11q remains unknown, we aimed to identify and compare the mi-croRNA expression profiles in HGBCL-11q, BL and in GCB-DLBCL-NOS. Next-generation sequencing (NGS)-based microRNA profiling of HGBCL-11q (n = 6), BL (n = 8), and GCB-DLBCL-NOS without (n = 3) and with MYC rearrange-ment (MYC-R) (n = 7) was performed. We identified sets of 39, 64, and 49 mi-croRNAs differentiating HGBCL-11q from BL, and from GCB-DLBCL-NOS without MYC-R, respectively. The expression levels of miR-223-3p, miR-193b-3p, miR-29b-3p, and miR-146a-5p consistently differentiated HGBCL-11q from both BL, GCB-DLBCL-NOS without MYC-R. In addition, HGBCL-11q presented greater heterogeneity in microRNA expression than BL. The expression profile of MYC-regulated microRNAs differed in HGBCL-11q and in BL, while also clearly distinguishing HGBCL-11q and BL from GCB-DLBCL-NOS. The microRNA pro-file of HGBCL-11q differs from those of BL and GCB-DLBCL-NOS, exhibiting greater heterogeneity compared to BL. The microRNA profile further supports that HGBCL-11q is a distinct subtype of B-cell lymphoma.

Critical Role of Extracellular Vesicles in Diffuse Large B-Cell Lymphoma; Pathogenesis, Potential Biomarkers, and Targeted Therapy-A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, characterized by its aggressive nature and heterogeneity. Despite significant advances in understanding DLBCL pathogenesis, there is still a need to elucidate the intricate mechanisms involved in disease progression and identify novel therapeutic targets. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators of intercellular communication in various physiological and pathological processes, including cancer. In recent years, evidence has suggested that EVs play a vital role in DLBCL biology by facilitating the exchange of genetic material, especially miRNAs, and proteins and lipids between tumor cells, immune cells, and the tumor microenvironment. We summarize and discuss the biological functions of EVs in DLBCL and their effects on the tumor microenvironment, highlighting their influence on DLBCL pathobiology, immune evasion, angiogenesis, and drug resistance. We also investigated EVs' diagnostic and prognostic potential as circulating biomarkers in DLBCL, emphasizing their utility in the non-invasive monitoring of the disease status and treatment response. Understanding the complex interplay between EVs and DLBCL may open up new avenues for personalized medicine, improve patient stratification, and facilitate the development of innovative therapeutic interventions in this devastating hematological malignancy.

Cuproptosis-related gene ATOX1 promotes MAPK signaling and diffuse large B-cell lymphoma proliferation via modulating copper transport.

Diffuse Large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin lymphoma, highlighting the importance of studying susceptibility genes to develop personalized treatment strategies. While cuproptosis, caused by high levels of copper ions induced by ionophores, has been shown to affect cancer survival, its specific role in lymphoma is not yet clear. To investigate the involvement of upregulation-related genes in DLBCL, we employed bioinformatics techniques. Specifically, we analyzed the differentially expressed genes (DEGs) in the GSE25638 dataset using Weighted Gene Co-expression Network Analysis (WGCNA) and performed functional enrichment analysis. By building a Protein-Protein Interaction (PPI) network, candidate genes were identified. Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curve analysis were used to confirm the clinical diagnostic use of these genes. The effects of Antioxidant 1 (ATOX1) knockdown, CuCl2, and DCAC50 treatments on DLBCL cells and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway were investigated by conducting in vitro experiments. Bioinformatics and in vitro experiments confirmed elevated expression of ATOX1 in DLBCL cells and tumor samples. ATOX1 knockdown led to decreased cell proliferation and G2 cell cycle arrest in vitro. Additionally, Phosphorylated Extracellular Signal-Regulated Kinases 1 and 2 (P-ERK1/2) protein levels within the MAPK pathway were reduced as a result of ATOX1 knockdown, but these levels were recovered by CuCl2. Treatment with DCAC50 showed a dose-dependent antiproliferative effect in DLBCL cells, which was strengthened by ATOX1 knockdown. Our study demonstrated that ATOX1 may be important in DLBCL via controlling the MAPK pathway through copper transport, providing new insights into potential therapeutic strategies for DLBCL.

Perspectives on the Mature T-Cell Lymphomas in the Middle East: A Comprehensive Review of the Present Status.

Background: T-cell lymphomas (TCLs) are rare and aggressive malignancies associated with poor outcomes, often because of the development of acquired drug resistance as well as intolerance to the established and often toxic chemotherapy regimens in elderly and frail patients. The many subtypes of TCL are well established to exhibit marked geographic variation. The epidemiology, clinical presentation, diagnosis, prognosis, and treatment of TCLs in the Middle East (ME) are yet to be explored; hence, limited data are available about these entities in this part of the world. Aim: Therefore, in this review article, we aim to discuss the available data regarding the T-cell neoplasms in the ME, including the incidence of specific subtypes of peripheral T-cell lymphoma (PTCL), as well as the trends in survival and treatment, all in an effort to understand the natural history of these complex entities across the ME.