The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco–Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients.
It is proposed that desiccation tolerance in the embryo of seeds depends upon the capacity to repair damage to genomic DNA when the desiccated embryo is rehydrated. From a study of imbibed and hydrated embryos of rye (Secale cereale) and wild oat (Avena fatua) evidence is provided that it is neither the extent of water uptake by the cells, the ensuing stability of the DNA to desiccation, nor the onset of S-phase DNA synthesis in the first cell cycle of germination that determines whether the desiccated embryo will survive. It is shown that when α- and β-polymerases of DNA repair are inhibited by aphidicolin and dideoxythymidine-5'-triphosphate, respectively, a γ-irradiation-induced DNA fragmentation cannot be fully repaired. It is shown that in hydrated embryos, at a stage when desiccation tolerance is lost, embryo cells still repair irradiation-induced damage, but this repaired DNA is unstable to desiccation and cannot be rerepaired when water is again made available. The failure to re-repair on rehydration appears to be critical to embryo survival and successful germination.
cells was significantly higher in MGUS (P = 0AE0005; mean 46AE4%) and MM patients (P £ 0AE0001; mean 57AE3%) than in reactive marrows (mean 2AE5%). FOXP2 (>10% nuclear positivity) was detectable in 90AE2% of MM (55/61) and 90AE9% of MGUS (10/11) patients, showing more frequent expression than CD56 and labelling 75% of CD56-negative MM (9/12). FOXP2 represents the first transcription factor whose expression consistently differentiates normal and abnormal plasma cells and FOXP2 target genes are implicated in MM pathogenesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.