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

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.

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.

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.

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.