Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA363009 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.
2017-04-30 | GSE93984 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.
2017-04-30 | GSE93985 | GEO
Project description:We established two representative ABC DLBCL cell lines (TMD8 and OCI-Ly10) with ibrutinib resistance by gradually increasing the concentration of ibrutinib during passage in culture. RNA-seq analysis demonstrated that the BCR pathway gene signature is enriched in resistant cell lines when compared to parental cells. The most upregulated gene is EGR1, a transcription factor that activates multiple oncogenic pathways including MYC and E2F. Elevated EGR1 expression is also observed in ibrutinib-resistant primary mantle cell lymphoma cells when treated with ibrutinib. Using multiple metabolic and genetic approaches, we discovered that overexpression of EGR1 causes metabolic reprogramming to oxidative phosphorylation (OXPHOS) and ibrutinib resistance. Mechanistically, EGR1 mediates metabolic reprogramming through transcriptional activation of PDP1, a phosphatase that dephosphorylates and activates the E1 component of the large pyruvate dehydrogenase complex. Therefore, EGR1-mediated PDP1 activation accelerates intracellular ATP production via the mitochondrial tricarboxylic acid (TCA) cycle, leading to sufficient energy to enhance the proliferation and survival of ibrutinib-resistant lymphoma cells. Finally, we demonstrate that targeting OXPHOS with IM156, a newly developed OXPHOS inhibitor, inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in patient-derived xenograft mouse models.
2023-12-06 | GSE223150 | GEO
Project description:To investagate the clinically observed BTK C481S, C481F, C481Y and C481R mutations in the regulation of B cell receptor signaling, we extablished TMD8 cells expressing BTK C481S, C481F, C481Y and C481R in which endogenous BTK was inactivated by ibrutinib. We then performed gene expression profiling analysis using data obtained from RNA-seq of 20 different cells after DMSO or 10 nM ibrutinib treatment from two indenpendent experiments.
2022-11-29 | GSE207322 | GEO
Project description:The goal of this study is to examine gene expression changes in TMD8 KLHL14(+/+) or TMD8 KLHL14(-/-) cells during ibrutinib treatment. The samples have 35 to 63 million pass filter reads with more than 92% of bases above the quality score of Q30.The average mapping rate of all samples is 95%. Unique alignment is above 86%. There are 3.65 to 6.25% unmapped reads.The mapping statistics are calculated using Picard software. The samples have between 0.86-1.29% ribosomal bases. Percent coding bases are between 58-62%. Percent UTR bases are 27-31%, and mRNA bases are between 87-90% for all the samples. We show that TMD8 KLHL14(-/-) cells have less down-regulation of NF-kB signatures and IL10/JAK1/STAT3 signatures upon ibrutinib treatment when compared to TMD8 KLHL14(+/+) cells.
2020-03-03 | GSE141143 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Expression data from Irinotecan resistant LoVo cells comapred to parental LoVo cells
| PRJNA255455 | ENA
Project description:Expression Data form parental vs. TAE684 resistant SH-SY5Y neuroblastoma cells
| PRJNA296540 | ENA
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Bruton Tyrosine Kinase (BTK) plays an essential role in signal transduction downstream of cell surface receptors on B lymphocytes, including the B-cell receptor (BCR), a key driver of several sub-types of human B-cell lymphoma and leukaemia. As such, BTK inhibitors have proven to be effective therapies for B-cell malignancies, most notably Ibrutinib. Targeted covalent inhibitors (TCIs) directing cysteine typically rely on a narrow set of electrophilic “warheads”. Michael acceptors remain at the forefront of TCI design strategies, yet have variable stability and selectivity under physiological conditions. Our RNA-Seq experiments were performed on TMD8 cells that had been cultured for 8 hours with DMSO, ibrutinib or 4 chemical constructs that we describe in Moraru et al. (2024), resulting in a total of 18 libraries. Our data show that the 2-sulfonylpyrimidine motif is an effective replacement for the acrylamide warhead of Ibrutinib.
2024-08-29 | E-MTAB-14363 | biostudies-arrayexpress