Targeted gene expression profiling as a tool for diagnostic cell-of-origin determination and prognostic...

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Diffuse large B-cell lymphoma (DLBCL) classification into activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subtypes is based on cell-of-origin (COO).
• While COO reflects distinct pathogenetic mechanisms, its prognostic significance is decreasing with new therapies.
• Molecular subtyping of DLBCL is emerging as a crucial tool for personalized treatment.

Purpose of the Study:

• To evaluate targeted gene expression profiling (GEP) for rapid and practical ABC/GCB classification and patient risk stratification in DLBCL.
• To compare GEP-based COO classification with immunohistochemical (IHC) methods.
• To develop a novel prognostic tool for DLBCL patient stratification.

Main Methods:

• Targeted GEP using a custom Lympho-qPCR panel on 89 DLBCL tissue samples.
• Analysis using three GEP-based classification models (A, B, and C).
• Parallel DNA sequencing (LYNX panel) for genetic aberration analysis in patients with early progression.

Main Results:

• GEP Model A showed moderate correlation (62%) with IHC COO determination.
• GEP Model B predicted COO independently of IHC.
• GEP Model C, an IHC-independent tool, identified high-risk patients with significantly worse outcomes, irrespective of clinical indicators.
• Genetic analysis revealed complex chromosomal aberrations and defects in BCL2, TP53, and CDKN2A/B in early progression cases.

Conclusions:

• Targeted GEP is a robust, rapid, and clinically applicable method for COO determination and risk stratification in DLBCL.
• The predictive value of ABC/GCB classification is expected to rise with novel targeted therapies.
• Integrating transcriptomic and genetic data is vital for individualized risk assessment in DLBCL molecular diagnostics.