Project description:Plasmablastic lymphoma has been scarcely studied because of its rarity. Transcriptomic studies are crucial to unveil the biology of this lymphoma. In particular, miRNA expression will help to understand the lymphomagenesis of plasmablastic lymphoma. We used microarrays to depict the miRNA expression landscape of plasmablastic lymphoma and to identify miRNAs differentially expressed compared to a control group.
Project description:Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma.
Project description:Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma. Expression profiles of 15 plasmablastic lymphomas and 10 diffuse large B-cell lymphomas were obtained using Afymmetrix U133A2 microarrays.
Project description:Plasmablastic lymphoma is an aggressive B-cell lymphoma with an immunoblastic/large cell morphology anda plasmacytic differentiation. The differential diagnosis with Burkitt lymphoma, plasma cell myeloma and some variants of diffuse large B-cell lymphoma may be challenging due to the overlapping morphological, genetic and immunophenotypic features. Furthermore, the profile of chromosomal alterations is not well known.
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
Project description:To determine differential expression of miRNA in classical Hodgkin lymphoma diseased nodes compared to non-malignant lymph nodes, we used agilent microarray release 16 and quantile normalisation using Genespring GX software to quantify and compare miRNA expression..
Project description:miRNA profiling has been performed on primary tumor samples collected at diagnosis from pediatric patients affected by T-cell lymphoblastic lymphoma.
Project description:To determine differential expression of miRNA in classical Hodgkin lymphoma diseased nodes compared to non-malignant lymph nodes, we used agilent microarray release 16 and quantile normalisation using Genespring GX software to quantify and compare miRNA expression.. Total RNA was extracted from 8 non-malignant lymph node and 14 classical Hodgkin lymphoma diseased node (6 mixed cellularity and 8 nodular sclerosing) formalin-fixed paraffin-embedded tissue samples