The Effects of MYC and BCL6 Rearrangements on The Molecular Profile of Diffuse Large B-cell Lymphomas, Not Otherwise Specified

Abstract

Background: Diffuse large B-cell lymphomas (DLBCL) are genetically heterogeneous and the most common subtype of Non-Hodgkin Lymphomas in adults. They account for approximately 40% of all B-cell lymphomas and more than 80% of all aggressive lymphomas worldwide. DLBCL harbouring MYC and/or BCL6 translocations were reported by studies using fluorescence in situ hybridisation to account for approximately 10% of DLBCL. We conducted a study investigating the proteomic and microRNA expression profiles of single- (MYCR or BCL6R) and dual- rearrangement (DR) (MYCRBCL6R) lymphomas. Methods: We employed Matrix-Assisted Laser Desorption Ionisation Imaging Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry for proteomic analysis and RT-qPCR for microRNA analysis. The study cohort consisted of three experimental groups including BCL6R (n=2), MYCR (n=4), and BCL6RMYCR (n=2). The study also included a control group which was the group with no translocation for both genes (n=8). To validate our findings, we utilised immunohistochemistry on the proteomics data and RT-qPCR for Let-7d and KRAS on the microRNA-related data. Results: Ten proteins belonging to the cytoskeletal family were differentially expressed between the experimental and control groups. These proteins differentiated between two groups with at least an area under the curve of 0,8. MiR-155-5p, miR-21- 5p, miR-29a-3p, miR-34a-5p, and the miR-17-92 cluster were dysregulated in the experimental groups. Conclusion: DLBCL, NOS with MYC and/or BCL6 translocations are associated with dysregulated miRNAs and proteins. These proteins are associated with NF-kB and BCR pathways, and developments of poor response or resistance to treatment. Decreased patient overall survival rate and increased poor prognosis can be attributed to rearrangements of MYC and BCL6.