This year’s American Association for Cancer Research(AACR) annual meetingtook 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 3 rdApril, 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.
- 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 vsafter transformation, miR-150 was significantly reduced
- miR-150 demonstrated significantly reduced expression in de novoDLBCL versusFL
- 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.