Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA182327 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. In these study we hypothesized that PIM kinases could be of therapeutic value in PTCL because we found an overexpression of PIM1 and PIM2, but not PIM3, in PTCL cases, cell lines and primary tumoral T cells from Sezary Syndrome patients, compared with reactive lymph nodes and normal T cells from healthy donors, respectively. In order to understand the mechanism of action of this pan-PIM inhibitor in PTCL, 4 cell lines (DERL7, HuT78, SR786 and MyLa) were treated with 10 μM of ETP-39010 for 0, 2, 4, 6, 10 and 24 h, and gene expression profiling was performed. 4 PTCL cell lines (DERL7, HuT78, SR786 and MyLa) were treated with DMSO and 10 μM of the pan-PIM inhibitor ETP-39010, and hybridized using the Universal Human Reference RNA (Stratagene, La Jolla, CA) as the reference sample.
2014-11-14 | E-GEOD-42595 | biostudies-arrayexpress
Project description:Gene expression profiling of diffuse large B-cell lymphoma (DLBCL)-derived cell lines exposed to the pan-PIM inhibitor MEN1703 was performed to investigate transcriptional consequences of PIM kinase inhibition in DLBCL and to identify treatment-related changes in the signalling pathways.
2021-10-12 | GSE158120 | GEO
Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. In these study we hypothesized that PIM kinases could be of therapeutic value in PTCL because we found an overexpression of PIM1 and PIM2, but not PIM3, in PTCL cases, cell lines and primary tumoral T cells from Sezary Syndrome patients, compared with reactive lymph nodes and normal T cells from healthy donors, respectively. In order to understand the mechanism of action of this pan-PIM inhibitor in PTCL, 4 cell lines (DERL7, HuT78, SR786 and MyLa) were treated with 10 μM of ETP-39010 for 0, 2, 4, 6, 10 and 24 h, and gene expression profiling was performed.
2014-11-14 | GSE42595 | GEO
Project description:The study uses RNA sequencing to profile AZD1208 resistant (AZDR) vs AZD1208 sensitive HSB-2 cells. PIM inhibitor treatment decreases leukemia burden in early T-cell precursor acute lymphoblastic leukemias (ETP-ALL) both in vitro and in vivo. However, prolonged treatment of ETP-ALL with PIM kinase inhibitors results in PIM inhibitor resistance. The analysis revealed that the HOXA9, mTOR, MYC, NF-B, and PI3K-AKT pathways were activated in PIM inhibitor resistant ETP-ALL
2021-09-20 | GSE135545 | GEO
Project description:T cell antigen-receptor (TCR) and cytokine receptor engagement trigger large changes in Serine/Threonine kinase signalling networks to drive T cell activation and differentiation. The role of only few kinase signalling pathways have been studied in detail, and in this context, Pim kinases are an interesting, yet understudied, family of Serine/Threonine kinases, with reported roles in key processes including survival, proliferation, metabolism across a range of cell types. T lymphocytes predominantly express PIM1 and PIM2, which are rapidly induced by TCR, costimulation and cytokine signalling. Using single shot DDA mass spectrometry we examine the impact of 24 hours treatment with two different pan-Pim kinase inhibitors PIM447 and AZD1208 on in vitro IL2 differentiated effector cytotoxic T lymphocytes. The Jak1/3 inhibitor tofacitinib was included as a control as this also blocks production of Pim kinases downstream of IL2. We find that treatment with pan-Pim kinase inhibitors has a similar phenotype to Pim1/Pim2 double deficiency, showing a reduction in proteins that are key for effector cell function: glucose transporters SLC2A1 and SLC2A3 and key effector molecule Granzyme B and an increase in the translational repressor PDCD4.
2024-04-15 | PXD051214 | Pride
Project description:PIM serine/threonine kinases are overexpressed, translocated or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types, and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBLC), follicular lymphoma (FL), marginal zone lymphoma-MALT type (MZL-MALT), chronic lymphocytic leukemia (CLL) and nodal marginal zone lymphoma (NMZL) cases. Increased PIM2 protein expression was associated with an aggressive clinical course in ABC-DLBCL patients. Pharmacological and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity, and indicated the involvement of PIM2 kinase in regulating mTORC1. The simultaneous genetic inhibition of all three PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification. Gene-expression profiling was conducted in a series of 114 B-cell non-Hodgkin lymphoma patients (DLBCL, FL, MALT, MCL, CLL and NMZL). Seven freshly frozen lymph nodes and six freshly frozen reactive tonsils were used as controls.
2011-10-16 | E-GEOD-32018 | biostudies-arrayexpress
Project description:PIM serine/threonine kinases are overexpressed, translocated or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types, and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBLC), follicular lymphoma (FL), marginal zone lymphoma-MALT type (MZL-MALT), chronic lymphocytic leukemia (CLL) and nodal marginal zone lymphoma (NMZL) cases. Increased PIM2 protein expression was associated with an aggressive clinical course in ABC-DLBCL patients. Pharmacological and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity, and indicated the involvement of PIM2 kinase in regulating mTORC1. The simultaneous genetic inhibition of all three PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.
2011-10-17 | GSE32018 | GEO
Project description:The overexpression of PIM kinases in hematologic malignancies, including multiple myeloma, make PIM inhibitors an attractive therapeutic strategy for these diseases. Recent preclinical data from our group demonstrated the anti-myeloma effect of the pan-PIM kinase inhibitor PIM447, along with its synergistic effect with standard of care anti-myeloma agents. Based on those previous data, we have evaluated here the in vitro and in vivo activity of the triple combination of PIM447 + pomalidomide + dexamethasone (PIM-Pd). Our results show that this combination exerts a potent anti-myeloma effect in vitro, even in presence of microenvironment cells, and, in vivo, it markedly delays tumor growth and prolongs survival. Mechanism of action studies suggest that the combination PIM-Pd inhibits protein translation processes through the convergent inhibition of mTORC1, which disrupts the function eIF4E, and c-Myc. As a consequence, cell cycle arrest and disruption of metabolic pathways, including glycolysis and lipid biosynthesis, is induced, inhibiting myeloma cell proliferation. Altogether, these data support the potential future clinical development of the triple combination PIM-Pd for the treatment of patients with MM.
2020-11-02 | GSE138440 | GEO
Project description:Cell lines representing human T-ALL were analyzed to compare GATA3low ETP-ALL (i.e. PER-117) with "typical" T-ALL. Moreover, changes in global gene expression were assessed comparing GATA3low ETP-ALL (i.e. PER-117) and GATA3high ETP-ALL (i.e. Loucy) upon treatment with Decitabine, a hypomethylating agent. Analysis of 6 human cell lines representing "typical" T-ALL (BE13, Jurkat, Molt4, RPM18402) and ETP-ALL (Loucy, PER-117). Additionally, global gene expression was assessed before and after treatment of ETP-ALL cell lines with Decitabine
2016-02-26 | E-GEOD-78166 | biostudies-arrayexpress
Project description:Activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is one the most frequent genetic events in human cancer. Therefore, the development of PI3K inhibitors has attracted much attention. We previously described the pyrazolopyrimidine derivative ETP-45658 as a potent inhibitor of PI3K p110α in vitro and in vivo. Here we report the gene expression signatures of MCF7 cells treated with ETP-45658 or the reference PI3K inhibitor PI-103. Both compounds potently inhibited proliferation of a wide range of human cancer cells. ETP-45658 most potently suppressed the growth of PIK3CA (E545K)-mutated MCF7 breast cancer cells. Treatment with ETP-45658 or PI-103 resulted in a time and concentration-dependent decrease in phosphorylation of AKT Ser473 in MCF7 cells. We conducted microarray analysis examining the gene expression profile in MCF7 cells at six hours post ETP-45658 or PI-103 incubation. Both compounds induced the expression of negative cell cycle regulators including Cyclin G2, p27kip1 and ING4 and decreased positive regulators such as Cyclin D1 without significantly affecting the expression of pro-apoptotic genes. We found FOXO transcription factor binding sites over-represented in both up- and down-regulated genes but not in those without significant changes. The expression of the breast cancer tumor suppressor Nischarin was found to be induced by ETP-45658 but not after PI-103 treatment while several genes differentially expressed specifically after ETP-45658 treatment are functionally associated with the focal adhesion pathway. Twelve samples have been analyzed in six different conditions. Two replicates have been included for each condition.
2014-04-08 | E-GEOD-56579 | biostudies-arrayexpress