Supplementary Data from Pan-HDAC Inhibitors Restore PRDM1 Response to IL21 in CREBBP-Mutated Follicular Lymphoma

Autor: Thierry Fest, Vincent Ribrag, Karin Tarte, Fabrice Jardin, Thierry Lamy, Pascal Godmer, Marc-Antoine Belaud-Rotureau, Catherine Henry, Gersende Caron, Valérie Camara-Clayette, Jérôme Le Priol, Eric Guiheneuf, Cédric Pastoret, Francisco Llamas-Gutierrez, Céline Pangault, Mikaël Roussel, Fabienne Desmots
Rok vydání: 2023
Popis: Figure S1 : (A) The 1769-genes signature corresponding to CB/CC transition and CB response to IL-21/CD40L co-stimulation and that are differentially expressed in FL compared to CC and CB were explored using Ingenuity Pathway Analysis (IPA). IPA enrichment analysis showed that these genes are mainly involved in CD40L signaling and IPA diagram highlight activated pathway including NF-KappaB (Nuclear Factor-KappaB), MAPK (Mitogen-Activated Protein Kinase) and STAT3 (Signal Transducers and Activators of Transcription-3). This observation suggests that FL-tumor cells can respond to the Il- 21/CD40L signaling. (B) Modulation of gene expression in CB compared to FL during CB/CC transition related to CD40L+IL-21 stimulation was explored by geneset enrichment assays (GSEA) using signatures available on MSigDB: M8493 for CD40 up-regulated genes, M2827 for IL-21 up-regulated genes, M4552 for up-regulated genes in plasma cells. (C) BLIMP-1 immnunostaining performed on multiple myeloma (1), reactive lymph node (2) and follicular lymphoma (3) gives strong, weak (very few positive cells) and negative signal respectively, using the PRDM1 antibody (3H2-E8) from Thermo Scientific. Figure S2: Burkitt lymphoma-derived L3055 cell line characteristics. Figure S3: Purity and viability of FL B-cell fractions. Figure S4: Visualization of gating strategy of a representative sample. Figure S5 : BCL6 binding analysis on Intron 3 of PRDM1 gene. Figure S6: Detection of PRDM1 mRNA and BLIMP1 protein in unstimulated or treated L3055 cells. Figure S7 : FL B cell number for each fraction and percentage of cell viability in each cell culture condition (N=6). Figure S8 : Uncropped original images of immunoblots. Table S1 : Top-20 pathways associated with 804-upregulated (upper panel) or 967-downregulated genes (lower panel). Table S2: Clinical data and somatic mutations for epigenetic genes - CREBBP, EP300, EZH2, KMT2D & MEF2B - in the 20 FLs of the cohort. Table S3: Available clinical data and somatic mutations found in genes designed in the lymphopanel for the 4 patients with a refractory or multiple relapsing FL tested for the oral administration of the HDACi treatment. Table S5: List of primers used for quantitative RQ-PCR and QChIP-PCR
Databáze: OpenAIRE