GENE EXPRESSION PROFILING OF <i>T</i>(14;18)‐NEGATIVE CD23+ FOLLICLE CENTER LYMPHOMA DEMONSTRATES ACTIVATION OF THE IL4/JAK/STAT6 PATHWAY AND A ROLE IN ITS PATHOGENESIS

Introduction: t(14;18)-neg FL cases show similar copy number alterations and mutations as carried by t(14;18)-pos FL, but with different frequencies. STAT6 are significantly more frequent in than correlate CD23 expression. The consequences of have not been investigated, the impact pathway activation on tumor microenvironment, which plays a central role largely unknown. (i.e., IL4R), demonstrated primary mediastinal large B-cell lymphoma (PMBL), underlying importance lymphomagenesis. aim this study was to perform gene expression profiling (GEP) well-characterized mutational analysis associated genes. Methods: GEP performed 52 including 39 or SOCS1 mutation (FLnegmut), 13 STAT6/SOCS1 wild type sequence (FLnegwt). Expression 1392 genes tumor/immune interaction investigated using HTG EdgeSeq Immuno-Oncology panel. DESeq2 algorithm used determine differentially expressed (p-adj < 0.05, fold change ≥1.5 ≤−1.5). Gene set enrichment (GSEA, Broad Institute) for performed. An Ampliseq custom panel explore (DUSP2, IL4R, IL13RA1, PTPN1, JAK1-3, STAT3, SOCS3, TYK2). Results: FLnegmut versus FLnegwt showed 32 In significant upregulation detected 23 (CD23, CD83, ALOX5, ELL3, CD40, NCF1, GPR18, CD20, CD22, CD180, HLA-DOB, CIITA, HLA-DMB, LTB, PIK3CG, PAX5, CLEC4A, SELL, TNFRSF17, WASHC4, IL13RA1) downregulation 9 (SLAMF7, FCRLA, TNFRSF13B, CHIT1, FCGR1A_FCGR1B, MNDA, S100A8, IRF4, FCGR3A_3B). FLnegmut, germinal center (GC) activated B cells (ABC) GPR18) were upregulated, whereas predominantly shows upregulated post-GCB IRF4), transcriptional program supporting plasma cell differentiation. contrast PMBL, no other identified. Conclusion: identified two distinct groups within indicating stages differentiation neoplastic cells. through IL4R GSEA correlates Constitutive consequent prevent ongoing precluding from exiting GC adopting state cell. contrast, suggesting that COO is late Keywords: indolent non-Hodgkin lymphoma, biology heterogeneity No conflicts interests pertinent abstract.