Abundant expression of BMI1 in follicular lymphoma is associated with reduced overall survival

Leuk Lymphoma. 2018 Sep;59(9):2211-2219. doi: 10.1080/10428194.2017.1410883. Epub 2017 Dec 18.

Abstract

Although generally indolent, follicular lymphoma (FL) sometimes pursues a more aggressive course leading to early death. B-cell-specific Mo-MLV insertion site-1 (BMI1) is a member of the polycomb group (PcG) proteins that confer stem cell properties through gene silencing. We used multi-channel immunofluorescence and automated image analysis to quantify BMI1 selectively in the nuclei of FL-derived B-cells in routine biopsy specimens. Applying this assay to 109 pretreatment FL biopsy samples demonstrates a significant association between abundant BMI1 and reduced overall survival (p = .001); the statistically significant association with mortality persists in a Cox proportional hazards model that includes Follicular Lymphoma International Prognostic Index (FLIPI) score, histological grade, and the presence of a component of diffuse large B-cell lymphoma in the biopsy sample. Ascertaining BMI1 over-expression may be useful in identifying patients who might benefit from novel therapies directed at reversing the chromatin-modifying functions of BMI1.

Keywords: BMI1; Follicular lymphoma; image analysis; immunofluorescence; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use
  • Cell Line, Tumor
  • Female
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Kaplan-Meier Estimate
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / metabolism
  • Lymphoma, Follicular / pathology
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Polycomb Repressive Complex 1 / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Rituximab / therapeutic use*

Substances

  • Antineoplastic Agents, Immunological
  • BMI1 protein, human
  • Rituximab
  • Polycomb Repressive Complex 1