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ARTICLE

Transcriptomic Study of Diffuse Large B-Cell Lymphoma Associated with HIV Infection: Identification of Novel Molecular Subtypes

Yasmine Labiad1, Céline Baier1, Michèle Genin2, Caroline Besson3,4, Sophie Prevot5, Hubert Lepidi6, Régis Costello1,7,*
1 Aix Marseille Univ, TAGC/INSERM UMR1090, Parc Scientifique de Luminy, Marseille, France
2 Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP) UMRS1136 INSERM et UPMC, Paris, France
3 Service d’Hématologie Oncologie, Centre Hospitalier de Versailles, Versailles, France
4 Centre de Recherche en Epidémiologie et Santé des Populations (CESP), INSERM U1018, Université Paris-Saclay, Villejuif, France
5 Service d’Anatomopathologie, AP-HP, Le Kremlin-Bicêtre, France
6 Service d’Anatomopathologie, AP-HM, CHU La Timone, Marseille, France
7 Service d’Hématologie et Thérapie Cellulaire, AP-HM, CHU La Conception, Marseille, France
* Corresponding Author: Régis Costello. Email: email

Oncology Research https://doi.org/10.32604/or.2026.076241

Received 17 November 2025; Accepted 29 April 2026; Published online 04 June 2026

Abstract

Objectives: Transcriptomic profiling has enabled the classification of Diffuse Large B-Cell Lymphoma (DLBCL) into distinct subtypes, such as Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC), primarily in HIV-negative patients. However, HIV-associated DLBCL may follow different molecular mechanisms due to immune dysregulation. This study aimed to characterize the transcriptomic landscape of HIV-related DLBCL to identify distinct subtypes and deregulated pathways with potential theranostic implications. Methods: Twelve formalin-fixed, paraffin-embedded DLBCL samples from HIV-positive patients were analyzed using Agilent’s microarray. Quantile normalization and unsupervised hierarchical clustering were performed to classify tumors based on gene expression profiles. Results: Two distinct transcriptomic subgroups were identified. TP53 and BCL7A were overexpressed in cluster I, while BCL2 was overexpressed in cluster II. Notably, the “immune system development” pathway was under expressed in cluster I compared to cluster II. Conclusions: Our findings reveal two molecularly distinct subtypes of HIV-associated DLBCL, likely driven by differences in tumor microenvironment and immune status. These transcriptomic profiles may guide future targeted therapies. Further validation in larger cohorts and integration with proteomic and clinical data are warranted to develop a comprehensive theranostic framework.

Graphical Abstract

Transcriptomic Study of Diffuse Large B-Cell Lymphoma Associated with HIV Infection: Identification of Novel Molecular Subtypes

Keywords

Diffuse large B-cell lymphoma; HIV-associated lymphoma; transcriptomic profiling; molecular subtypes; gene expression analysis; biomarker discovery

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