Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA102421 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Currently there is no method available to predict response to farnesyltransferase inhibitors (FTI). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib, in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1:APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy. This two-gene ratio was validated by quantitative PCR (QPCR) in the newly diagnosed AML cohort. We further demonstrated that this classifier could predict response to tipifarnib in an independent set of 54 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days, p = 0.0001), which was shown to be independent of other prognostic factors including a previously described gene expression classifier predictive of overall survival. Therefore, these data indicate that a two-gene expression assay may have utility in categorizing a population of AML patients who are more likely to respond to tipifarnib. Experiment Overall Design: 34 samples from 34 patients
2008-06-17 | E-GEOD-8970 | biostudies-arrayexpress
Project description:Currently there is no method available to predict response to farnesyltransferase inhibitors (FTI). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib, in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1:APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy. This two-gene ratio was validated by quantitative PCR (QPCR) in the newly diagnosed AML cohort. We further demonstrated that this classifier could predict response to tipifarnib in an independent set of 54 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days, p = 0.0001), which was shown to be independent of other prognostic factors including a previously described gene expression classifier predictive of overall survival. Therefore, these data indicate that a two-gene expression assay may have utility in categorizing a population of AML patients who are more likely to respond to tipifarnib. Keywords: classification
2007-09-12 | GSE8970 | GEO
Project description:Data dependent analysis of acute myeloid leukemia samples in the presence and absence of the serine protease inhibitor DFP
2023-07-26 | MSV000092526 | MassIVE
Project description:We utilize the syngeneic 9464D-GD2 mouse model to investigate the role of neuroblastoma-derived small extracellular vesicles (sEVs) in developing resistance to the anti-GD2 monoclonal antibody dinutuximab. RNA-sequencing and flow cytometry analysis of whole tumors revealed that neuroblastoma-derived sEVs modulate immune cell tumor infiltration upon dinutuximab treatment to create an immunosuppressive tumor microenvironment that contains more tumor-associated macrophages (TAMs) and fewer tumor-infiltrating NK cells. Importantly, tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion, drastically enhanced the efficacy of dinutuximab and reversed the immunosuppressive effects of neuroblastoma-derived sEVs.
2022-05-04 | GSE189921 | GEO
Project description:Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again.
2012-09-30 | GSE37286 | GEO
Project description:Notch-targeted gamma-secretase inhibitors (GSIs) exhibited limited efficacy in glioblastoma patients. We identified that farnesyltransferase inhibitors (FTIs) increased sensitivity to GSIs in glioblastoma stem cells. To interrogate the mechanisms mediating the interaction between these two classes of compounds, we studied the impact on gene expression profiles by the combination of tipifarnib (FTI) and RO4929097 (GSI). We found that this combination treatment significantly suppressed genes implicated cell cycle progression. Real-time PCR validated the activities of tipifarnib to modulate expression of cell cycle regulators. We also showed that RO4929097 sensitized glioblastoma stem cells to compounds targeting some of these cell cycle regulators, such as AURKB and CDK4/6. These results suggest that regulation of cell cycle progression partially mediates the ability of FTIs to sensitize glioblastoma stem cells to GSIs.
2017-10-11 | GSE104783 | GEO
Project description:Targeted next-generation sequencing was performed in patients with IDH2-mutant acute myeloid leukemia to identify genomic mechanisms of primary or acquired resistance to the mutant IDH2 inhibitor enasidenib.
2018-04-20 | PRJEB26337 | EVA
Project description:Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again. We used two different pre-B ALL cell lines 8093 and Bin-2, derived from two BCR/ABL transgenic mice. 8093 is a leukemia on an inbred f11 C57Bl/6J background whereas Bin2 was derived from ALL on a mixed genetic background. Each was treated with the tyrosine kinase inhibitor nilotinib = AMN107 (20 nM for 8093, 50 nM for Bin-2, abbreviated with nil or n) or with the farnesyltransferase inhibitor (FTI) Lonafarnib/SCH66336 (1 mM for 8093, 0.25 mM for Bin-2; abbreviated with lon or l) in the presence of an irradiated mouse embryonic fibroblast feeder layer. Cells loosely attached to the top of the feeder layer or present in the medium were harvested for RNA isolation. Except where noted, all samples were taken in biological triplicates (separate plates). Samples were taken at t=0 (begin/start); on day 3 for Bin-2 (nil and lon) when the viability was 5-10% based on Trypan blue exclusion, on d4 for 8093 (lon, viability 20%) or d3 (nil, 5-10% viability) at the midpoint when cells start to develop resistance, and on d30 (Bin-2 x lon), d21 (Bin-2 x nil), d26 (8093 x lon) and d 20 (8093 x nil) when the viability of the culture was completely restored (around 90% viability), and the cells started proliferating agin in the presence of the drug. Cells were kept in the presence of drug throughout the entire treatment, which was added fresh with medium changes. The same feeder layer was kept during the entire period.
2012-09-30 | E-GEOD-37286 | biostudies-arrayexpress
Project description:Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) is guided by the pre-defined European Leukemia Net (ELN) or other response criteria. This allows patient stratification only during but not prior to treatment initiation. Gene expression profiling (GEP)-based response prediction might become a valuable tool for patient stratification in CML, but so far published data for response prediction are conflicting. We generated an imatinib response predicting gene signature by GEP from peripheral blood samples of pre-treated CML patients in late chronic phase.
2021-12-31 | GSE44589 | GEO
Project description:Acute myeloid leukemia cell line THP1 immunopeptidome HLA A2 specific
2021-02-22 | MSV000086922 | MassIVE