DLBCL|FL

AACR 2017 poster 1479/21 – Differential expression of microRNAs in transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

This year’s American Association for Cancer Research (AACR) annual meeting took place on 1–5 April in Washington, DC, USA. The program committee Chair was Kornelia Polyak, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts.

On Monday 3rd April, a poster (1479 / 21) by Katerina Musilova, from Ceitec MU, Faculty of Medicine MU, and University Hospital Brno, Czech Republic, et al. titled “Differential expression of microRNAs in transformation of follicular lymphoma to diffuse large B cell lymphoma” was presented.

The group explored the role of miRNAs in the transformation of indolent FL into aggressive DLBCL; transformation occurs in around 3% of cases per year and has a median survival of only 2 years.

Key Highlights:
  • NGS found many aberrations associated with transformed FL (tFL), such as frequent high-level activity of MYC (amplifications, translocations, and mutations) or loss of DNA damage regulators (p53, CDKN2A/B)
  • miRNA profiling in paired FL and tFL samples (n = 8 pairs) of 380 miRNAs revealed 5 miRNAs that are expressed differently in tFL (P < 0.05, fold-change >1.8)
  • Most significant change was reduction in expression of miR-150 (~5-fold; P = 0.01)
  • In an independent cohort of non-paired samples of FL before vs after transformation, miR-150 was significantly reduced
  • miR-150 demonstrated significantly reduced expression in de novo DLBCL versus FL
  • miR-150 expression was reduced in patients with a FLIPI ≥3 (P = 0.03), with >20% Ki67 positivity (P = 0.003); low miR-150 associated with shorter OS
  • Expression of miRNA is down-modulated by B-cell adhesion to HS-S stromal cells in co-culture in vitro; suggesting its normal physiological function may relate to regulation of B-cell functions in the context of immune niches, potential contributing to FL progression and transformation
  • miR-150 was found to regulate BCR responsiveness in Lymphoma B-cells by targeting GAB1

The poster was concluded by stating that expression of miR-150 reduced during transformation of FL to DLBCL; low miR-150 expression correlated with high FLIPI score and Ki67 levels. The group are conducting additional investigations exploring to what extent miR-150 expression reduction is causally responsible for aggressiveness/transformation of FL.

Reference:
  1. Musilova K. et al. Differential expression of microRNAs in transformation of follicular lymphoma to diffuse large B cell lymphoma [Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [1479 / 21].