Similar Datasets
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma that originates from T follicular helper (Tfh) cells and is characterized by a prominent tumor microenvironment (TME). IDH2 and TET2 mutations co-occur frequently in AITL but their contribution to tumorigenesis is poorly understood. We have developed an AITL mouse model that is driven by Idh2 and Tet2 mutations and in which Tfh cells exhibit aberrant transcriptomic and epigenetic programming. Neoplastic Tfh cells bearing combined Idh2 and Tet2 mutations show altered crosstalk with normal germinal center B cells that promotes B clonal expansion while decreasing Fas-FasL interaction and reducing B cell apoptosis. This altered Tfh-B cell communication could explain the unique relationship between Idh2 mutation and the prototypical AITL TME. Our mouse model also recapitulates important features of human IDH2-mutated AITL, providing a rationale for exploring the therapeutic targeting of Tfh-TME crosstalk for AITL treatment.
2023-02-01 | GSE221599 | GEO
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma that originates from T follicular helper (Tfh) cells and is characterized by a prominent tumor microenvironment (TME). IDH2 and TET2 mutations co-occur frequently in AITL but their contribution to tumorigenesis is poorly understood. We have developed an AITL mouse model that is driven by Idh2 and Tet2 mutations and in which Tfh cells exhibit aberrant transcriptomic and epigenetic programming. Neoplastic Tfh cells bearing combined Idh2 and Tet2 mutations show altered crosstalk with normal germinal center B cells that promotes B clonal expansion while decreasing Fas-FasL interaction and reducing B cell apoptosis. This altered Tfh-B cell communication could explain the unique relationship between Idh2 mutation and the prototypical AITL TME. Our mouse model also recapitulates important features of human IDH2-mutated AITL, providing a rationale for exploring the therapeutic targeting of Tfh-TME crosstalk for AITL treatment.
2023-02-01 | GSE221600 | GEO
Project description:Background: Angioimmunoblastic T-cell lymphoma (AITL) is a malignancy with very poor survival outcome, in need of new more specific therapeutic regimen. The drivers of malignancy in this disease are CD4+ follicular helper T cells (Tfh). The metabolism of these malignant Tfh cells was not yet elucidated. Therefore, we decided to identify their metabolic requirements with the objective to propose a novel therapeutic option. Methods: To reveal the prominent metabolic pathways used by the AITL lymphoma cells, leveraged on our previously established AITL mouse model by crossing metabolomic and proteomic data of murine AITL cells. We confirmed these results using AITL patient and healthy T cell expression data. Results: Strikingly, the mAITL Tfh cells were highly dependent on the second branch of the Kennedy pathway, the choline lipid pathway, responsible for the production of the major membrane constituent phosphatidylcholine. Moreover, gene expression data from Tfh cells isolated from AITL patient tumors, confirmed the upregulation of the choline lipid pathway. Several enzymes involved in this pathway such as choline kinase, catalyzing the first step in the phosphatidylcholine pathway, respectively, are upregulated in multiple tumors other than AITL. Here we showed that treatment of our mAITL preclinical mouse model with the fatty acid oxydation inhibitor, etomoxir, significantly increased their survival and even reverted the exhausted CD8 T cells in the tumor into potent cytotoxic anti-tumor cells. Specific inhibition of Chok confirmed the importance of the phosphatidylcholine production pathway in the neoplastic CD4+ T cells, since it irradicated almost all the mAITL Tfh cells from the tumors. Finally, the same inhibitor induced in human AITL lymphoma biopsies cell death of the majority of the hAITL PD-1high neoplastic cells. Conclusion: Our results suggest that interfering with the choline metabolism in AITL might represent a new therapeutic strategy for these patients.
2024-04-04 | PXD046786 | Pride
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma that originates from T follicular helper (Tfh) cells and is characterized by a prominent tumor microenvironment (TME). IDH2 and TET2 mutations co-occur frequently in AITL but their contribution to tumorigenesis is poorly understood. We have developed an AITL mouse model that is driven by Idh2 and Tet2 mutations and in which Tfh cells exhibit aberrant transcriptomic and epigenetic programming. Neoplastic Tfh cells bearing combined Idh2 and Tet2 mutations show altered crosstalk with normal germinal center B cells that promotes B clonal expansion while decreasing Fas-FasL interaction and reducing B cell apoptosis. This altered Tfh-B cell communication could explain the unique relationship between Idh2 mutation and the prototypical AITL TME. Our mouse model also recapitulates important features of human IDH2-mutated AITL, providing a rationale for exploring the therapeutic targeting of Tfh-TME crosstalk for AITL treatment.
2023-02-01 | GSE221604 | GEO
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma that originates from T follicular helper (Tfh) cells and is characterized by a prominent tumor microenvironment (TME). IDH2 and TET2 mutations co-occur frequently in AITL but their contribution to tumorigenesis is poorly understood. We have developed an AITL mouse model that is driven by Idh2 and Tet2 mutations and in which Tfh cells exhibit aberrant transcriptomic and epigenetic programming. Neoplastic Tfh cells bearing combined Idh2 and Tet2 mutations show altered crosstalk with normal germinal center B cells that promotes B clonal expansion while decreasing Fas-FasL interaction and reducing B cell apoptosis. This altered Tfh-B cell communication could explain the unique relationship between Idh2 mutation and the prototypical AITL TME. Our mouse model also recapitulates important features of human IDH2-mutated AITL, providing a rationale for exploring the therapeutic targeting of Tfh-TME crosstalk for AITL treatment.
2023-02-01 | GSE221602 | GEO
Project description:miRNA differential expression in Rheumatoid arthritis(RA) blood: Microarray analysis of miRNAs in blood from RA and healthy donors.
2016-09-06 | GSE18097 | GEO
Project description:Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles which each subset plays in autoimmunity are not well studied. To compare the gene expression profiling 1) on intermediate monocytes CD14++CD16+ monocytes between healthy donors and autoimmune uveitis patients and 2) among 3 monocyte subsets in health donors, here we purified circulating intermediate CD14++CD16+ monocytes from 5 patients with autoimmune uveitis (labeled as P1-5) and 4 healthy donors (labeled as HD1-4) by flow cytometry and isolated total RNA to proceed microarray assay. In addition, we also purified CD14+CD16++ (non-classical monocytes) and CD14++CD16- (classical monocytes) from 4 healthy donors to do microarray. We demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar gene expression profile. The CD14+CD16++ cells (non-classical monocytes) display the most distinctive gene expression profiling when compared to intermediate CD14++CD16+ monocytes and classical CD14++CD16- monocytes.
2015-03-17 | GSE66936 | GEO
Project description:Platelets can change their expression of mRNA and miRNAs when educated by tumors. In this assay we assesed the diferential expression of miRNA between healthy individuals and patients suffering pancreatic cancer (PDAC) Platelets form 4 healthy donors, 4 PDAC patient blood and 4 PDAC patient pancreatic drainage were collected to asses differential expression
2022-05-17 | GSE203122 | GEO
Project description:Transcriptional profiling of human T cells analyzing the impact of race on the responsiveness to IFNa in healthy blood donors. Control and IFNa-treated samples derived from healthy Caucasian American vs. African American blood donors are compared.
2010-01-27 | GSE17952 | GEO
Project description:To identify the top 20 up-regulated genes in CD34+ cells from AML patients in comparison with healthy donors, we examined the microarray gene expression profile of CD34+ blasts from patients with newly diagnosed AML vs CD34+ normal cells from healthy donors. Despite the fact that combined therapy of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or chemotherapy dramatically improves the prognosis of patients with APL, these regimens can cause systemic infections and secondary leukemias. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARa and suppressing its sumoylation, ubiquitylation and degradation. This represses PML nuclear body assembly, p53-mediated senescence, cell differentiation, and supports cellular self-renewal. Genetically inhibiting Trib3 expression or disturbing the TRIB3/PML-RARa interaction produces potent therapeutic efficacy against APL and has synergic anti-APL effects when used in combination with ATRA or ATO by promoting PML-RARa degradation and PML expression. Our study provides new insight into APL pathogenesis and a new therapeutic option against APL.
2017-05-12 | GSE90062 | GEO