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Simple Summary: This research aims to identify new protein markers that can help predict the risk of disease progression in patients with follicular lymphoma (FL) at the time of diagnosis. By analyzing a large number of proteins in FL samples, the study found significant differences in protein composition among patients, which may help distinguish those at higher risk of disease progression. These findings could improve our understanding of FL biology and lead to the discovery of new biomarkers or treatment targets, potentially allowing for more personalized and effective treatment strategies for FL patients, improving their outcomes. Background: Follicular lymphoma (FL) is characterized by an indolent nature and generally favorable prognosis, yet poses a particular clinical challenge, since disease progression is observed in a notable subset of patients. Currently, it is not possible to anticipate which patients will be at risk of progression, highlighting the need for reliable predictive biomarkers that can be detected early in the disease. Methods: We applied tandem-mass-tag labelled nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) on 48 diagnostic formalin-fixed, paraffin-embedded tumor samples from patients with advanced-stage FL. Of these, 17 experienced subsequent progression (subsequently-progressing, sp-FL) while 31 did not (non-progressing, np-FL). Results: We identified 99 proteins that were significantly differentially expressed between sp-FL samples and np-FL samples (p < 0.05; log2-fold changes between 0.2 and −1.3). Based on this subset of proteins, we classified patients into high-risk and low-risk subgroups using unsupervised machine learning techniques. Pathway analyses of the identified proteins revealed aberrancies within the immune system and cellular energy metabolism. In addition, two proteins were selected for immunohistochemical evaluation, namely stimulator of interferon genes 1 (STING1) and isocitrate dehydrogenase 2 (IDH2). Notably, IDH2 retained significantly lower expression levels in sp-FL samples compared with np-FL samples (p = 0.034). Low IDH2 expression correlated with shorter progression-free survival (PFS, p = 0.020). Conclusions: This study provides evidence for some of the biological mechanisms likely to be involved in FL progression and, importantly, identifies potential predictive biomarkers for improvement of risk stratification up-front at time of FL diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Follicular lymphoma (FL) is an indolent, yet generally incurable neoplasia with a median survival exceeding 10 years. However, a subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, in the majority of cases to diffuse large B-cell lymphoma (DLBCL). This affects both the clinical course and the prognostic outcome, resulting in a markedly reduced survival after transformation. Thus, early risk stratification and prediction of patients at risk of HT would be highly valuable in the clinical setting. Here, we investigated the potential of the immune inhibitory programmed death 1 (PD-1) receptor as a biomarker predictive of HT. Patients and Methods: Immunohistochemical staining and quantification by digital image analysis of PD-1 was performed on diagnostic tumor-tissue samples from FL patients with and without subsequent transformation (n=34 and n=46, respectively), and on paired samples from the transformed lymphoma (n=34). Results: At the time of initial FL diagnosis, samples from patients with subsequent HT had significantly higher tumor-tissue expression of PD-1 compared with diagnostic FL samples from patients without subsequent HT (p=0.010). At the time of transformation, PD-1 expression was significantly reduced (p< 0.001). No difference was observed in intra-follicular PD-1 expression at FL diagnosis between samples from patients with or without HT; however, high intra-follicular levels of PD-1 were associated with significantly shorter transformation-free survival times (p< 0.043). Conclusion: Our data suggest that pre-treatment tumor-tissue PD-1 expression already predicts the risk of subsequent transformation to DLBCL, as early as the time of FL diagnosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression‐free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin‐fixed paraffin‐embedded lymphoma lymph node samples from CHL patients were analyzed by nano‐liquid chromatography–tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG‐avid lesions on a diagnostic FDG‐PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin‐converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha‐X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients. [ABSTRACT FROM AUTHOR]

Objective: Individuals with human immunodeficiency virus (HIV) experience an increased risk of lymphoma, making this an important cause of death among people with HIV. Nevertheless, little is known regarding the underlying genetic aberrations, which we therefore set out to characterize., Design: We conducted next-generation panel sequencing to explore the mutational status of diagnostic lymphoma biopsies from 18 patients diagnosed with lymphoma secondary to HIV infection., Methods: Ion Torrent next-generation sequencing was performed with an AmpliSeq panel on diagnostic lymphoma biopsies from HIV-associated B-cell lymphomas (n = 18), comprising diffuse large B-cell lymphoma (n = 9), classic Hodgkin lymphoma (n = 6), Burkitt lymphoma (n = 2), follicular lymphoma (n = 1), and marginal zone lymphoma (n = 1). The panel comprised 69 lymphoid- and/or myeloid-relevant genes, in which either the entire coding sequence or a hotspot region was sequenced., Results: Among the 18 lymphomas, we detected 213 variants. The number of detected mutations ranged from 4 to 41 per tumor distributed among 42 genes, including both exonic and intronic regions. The most frequently mutated genes included KMT2D (67%), TNFAIP3 (50%), and TP53 (61%). Notably, no gene was found to harbor variants across all the HIV-associated lymphomas, nor did we find subtype-specific variants. While some variants were shared among patients, most were unique to the individual patient and were often not reported as malignant genetic variants in databases., Conclusion: Our findings demonstrate genetic heterogeneity across histological subtypes of HIV-associated lymphomas and thus help elucidate the genetics and pathophysiological mechanisms underlying the disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)