BCL6 as a therapeutic target for lymphoma

Leeman‐Neill, Rebecca J.; Bhagat, Govind

doi:10.1080/14728222.2018.1420782

Cited by 64 publications

(61 citation statements)

References 91 publications

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“…Finally, we found a significant downregulation BCL6 (1.5-fold, p = 0.001) in SUDHL5 (Additional file 1: Table S1), in agreement with a very recent study demonstrating romidepsin-mediated depletion of BCL6 in B-cell lymphoma cells [39]. BCL6 is a central mediator of germinal center formation [40] and has been suggested as a therapeutic target in lymphoma [41].…”

Section: Sudhl5 (Logsupporting

confidence: 91%

HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines

et al. 2020

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Background: HDAC inhibitors (HDACi) belong to a new group of chemotherapeutics that are increasingly used in the treatment of lymphocyte-derived malignancies, but their mechanisms of action remain poorly understood. Here we aimed to identify novel protein targets of HDACi in Band T-lymphoma cell lines and to verify selected candidates across several mammalian cell lines. Methods: Jurkat T-and SUDHL5 B-lymphocytes were treated with the HDACi SAHA (vorinostat) prior to SILAC-based quantitative proteome analysis. Selected differentially expressed proteins were verified by targeted mass spectrometry, RT-PCR and western analysis in multiple mammalian cell lines. Genomic uracil was quantified by LC-MS/MS, cell cycle distribution analyzed by flow cytometry and class switch recombination monitored by FACS in murine CH12F3 cells. Results: SAHA treatment resulted in differential expression of 125 and 89 proteins in Jurkat and SUDHL5, respectively, of which 19 were commonly affected. Among these were several oncoproteins and tumor suppressors previously not reported to be affected by HDACi. Several key enzymes determining the cellular dUTP/dTTP ratio were downregulated and in both cell lines we found robust depletion of UNG2, the major glycosylase in genomic uracil sanitation. UNG2 depletion was accompanied by hyperacetylation and mediated by increased proteasomal degradation independent of cell cycle stage. UNG2 degradation appeared to be ubiquitous and was observed across several mammalian cell lines of different origin and with several HDACis. Loss of UNG2 was accompanied by 30-40% increase in genomic uracil in freely cycling HEK cells and reduced immunoglobulin class-switch recombination in murine CH12F3 cells. Conclusion: We describe several oncoproteins and tumor suppressors previously not reported to be affected by HDACi in previous transcriptome analyses, underscoring the importance of proteome analysis to identify cellular effectors of HDACi treatment. The apparently ubiquitous depletion of UNG2 and PCLAF establishes DNA base excision repair and translesion synthesis as novel pathways affected by HDACi treatment. Dysregulated genomic uracil

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Section: Sudhl5 (Logsupporting

confidence: 91%

HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines

et al. 2020

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“…NONMMUT008951.2 was located in Bcl11a which inhibited proliferation and promoted apoptosis in B lymphoma cell lines [21]. NONMMUT026003.2, in the ceRNA network of differentially expressed lncRNAs, was located Bcl6 which participated humorous of processes, including in ammatory response, growth and differentiation [22].…”

Section: Discussionmentioning

confidence: 99%

Lncrna-Associated Cerna Networks in Spleen of Nocth1-Correlated T-all Leukemia Mice

Shi

Wang

et al. 2020

Preprint

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BackgroundAcute T-lymphocytic leukemia (T-ALL) is a highly aggressive malignant tumor in leukemia.Nocth1 is considered as an major oncogene in the development of T-ALL. Increasing evidences have revealed that the occurrence and progression of T-ALL referred to abnormal gene expression, pathway activation and the regulation between these genes. However, the potential lncRNA-associated competing endogenous RNA (ceRNA) network involved in spleen of Nocth1-correlated T-ALL leukemia mice remains unclear.ResultsThe deep RNA-sequencing analysis shown that 1833 lncRNAs and 4626 mRNAs were deregulated according to the P-value (p<0.05) and fold change (>2-fold) in spleen of T-ALL leukemia mice compared with that of C57BL/6 mice. Gene Ontology(GO) and KEGG pathway analysis were performed to reveal the potential roles of differentiated expressed lncRNAs. Co-expression Network was performed to reveal the regulation relationship between the differentiated expressed lncRNAs and mRNAs. CeRNA prediction constructed the lncRNA-miRNA-mRNA model to find the core ceRNA based on regression model analysis and seed sequence matching methods.ConclusionThis study provided a systematic overview of the altered lncRNAs and mRNA expression, pathway and ceRNA regulation network in the pathogenesis of Nocth1-correlated T-ALL.

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“…NONMMUT008951.2 was located in Bcl11a which inhibited proliferation and promoted apoptosis in B lymphoma cell lines [21]. NONMMUT026003.2, in the ceRNA network of differentially expressed lncRNAs, was located Bcl6 which participated humorous of processes, including inflammatory response, growth and differentiation [22].…”

Section: Discussionmentioning

confidence: 99%

lncRNA-Associated ceRNA Networks in Spleen of Nocth1-correlated T-ALL Leukemia Mice

Shi

Wang

et al. 2020

Preprint

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Background Acute T-lymphocytic leukemia (T-ALL) is a highly aggressive malignant tumor in leukemia. Nocth1 is considered as an major oncogene in the development of T-ALL. Increasing evidences have revealed that the occurrence and progression of T-ALL referred to abnormal gene expression, pathway activation and the regulation between these genes. However, the potential lncRNA-associated competing endogenous RNA (ceRNA) network involved in spleen of Nocth1-correlated T-ALL leukemia mice remains unclear. Methods Overexpression of Notch intracellular domain (ICN) of Notch1 by retroviral infection was used to set up mouse T-ALL model. Deep RNA-sequencing analysis was performed the expression of lncRNAs and mRNA in spleen of T-ALL mice and C57BL/6 mice. Results The deep RNA-sequencing analysis shown that 1833 lncRNAs and 4626 mRNAs were deregulated according to the P-value (p<0.05) and fold change (>2-fold) in spleen of T-ALL leukemia mice compared with that of C57BL/6 mice. Gene Ontology(GO) and KEGG pathway analysis were performed to reveal the potential roles of differentiated expressed lncRNAs. Co-expression Network was performed to reveal the regulation relationship between the differentiated expressed lncRNAs and mRNAs. CeRNA prediction constructed the lncRNA-miRNA-mRNA model to find the core ceRNA based on regression model analysis and seed sequence matching methods. Conclusion This study provided a systematic overview of the altered lncRNAs and mRNA expression, pathway and ceRNA regulation network in the pathogenesis of Nocth1-correlated T-ALL.

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BCL6 as a therapeutic target for lymphoma

Cited by 64 publications

References 91 publications

HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines

HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines

Lncrna-Associated Cerna Networks in Spleen of Nocth1-Correlated T-all Leukemia Mice

lncRNA-Associated ceRNA Networks in Spleen of Nocth1-correlated T-ALL Leukemia Mice

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