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Biomarkers Informed by Single-Cell and Spatial Transcriptomics-Biomarkers for Grade 3 Follicular Lymphoma.

Aarti Kanzaria1, Sonali Arora2, Anisha Naik1

  • 1Naresh Lab, Pathology Program, Translational Science & Therapeutics Division, Fred Hutchinson Cancer Center, Seattle.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|January 11, 2026
PubMed
Summary
This summary is machine-generated.

New biomarkers like AICDA (AID) can objectively identify Grade 3 follicular lymphoma (FL), improving risk stratification and prognosis. These findings enhance grading reproducibility for better patient outcomes.

Keywords:
biomarkerfollicular lymphomagradingimmunohistochemistrylymphomatranscriptomics

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Follicular lymphoma (FL) outcomes vary, necessitating improved risk stratification biomarkers.
  • Current FL grading relies on subjective centroblast counts, leading to poor reproducibility.
  • Grade 3 FL is associated with a worse prognosis, highlighting the need for objective grading methods.

Purpose of the Study:

  • To identify objective biomarkers for centroblasts and centrocytes to enhance FL prognostication.
  • To develop reproducible methods for assessing FL grade and predicting patient outcomes.

Main Methods:

  • Reanalysis of public spatial and single-cell transcriptomic data from normal germinal centers and FL samples.
  • Validation of gene expression findings using immunohistochemistry (IHC) on FL specimens.
  • Receiver operating characteristic (ROC) curve analysis to determine optimal biomarker cut-offs.

Main Results:

  • AICDA (AID) and CXCR4 were identified as centroblast markers; CD40 and TFRC (CD71) as centrocytemarkers.
  • Grade 3 FL showed significantly higher expression of AID, CD71, and Ki67 compared to grade 1-2 FL.
  • AID demonstrated the best discriminatory ability for distinguishing FL grades, with reproducible assessment via digital and visual methods.

Conclusions:

  • AID, CXCR4, CD71, and Ki67 are promising objective biomarkers for FL grade 3 identification.
  • These biomarkers can potentially improve grading reproducibility and serve as independent prognostic tools.
  • Further clinical validation in uniformly treated FL cohorts is warranted to confirm prognostic value.