Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA84963 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To elucidate the genomics of cellular responses to cancer treatment, we analyzed the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination. Based on changes in gene expression, we identified 124 genes that accurately discriminated among the four treatments. Discriminating genes included those involved in apoptosis, mismatch repair, cell cycle control and stress response. Only 14% of genes that changed when these medications were given as single agents also changed when they were given together. These data indicate that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment, that changes in gene expression are treatment-specific and that gene expression can illuminate differences in cellular response to drug combinations versus single agents.
2007-12-13 | E-GEOD-412 | biostudies-arrayexpress
Project description:To elucidate the genomics of cellular responses to cancer treatment, we analyzed the expression of over 9,600 human genes in acute lymphoblastic leukemia cells before and after in vivo treatment with methotrexate and mercaptopurine given alone or in combination. Based on changes in gene expression, we identified 124 genes that accurately discriminated among the four treatments. Discriminating genes included those involved in apoptosis, mismatch repair, cell cycle control and stress response. Only 14% of genes that changed when these medications were given as single agents also changed when they were given together. These data indicate that lymphoid leukemia cells of different molecular subtypes share common pathways of genomic response to the same treatment, that changes in gene expression are treatment-specific and that gene expression can illuminate differences in cellular response to drug combinations versus single agents. Keywords: other
2003-04-21 | GSE412 | GEO
Project description:Genome-wide assessment of gene expression in primary acute lymphoblastic leukemia cells was performed to identify genomic determinants of MTX’s antileukemic effects. Reduction of circulating leukemia cells after in vivo methotrexate treatment served as a measure MTX's antileukemic effects. Keywords: gene expression associated with drug response
2008-03-15 | GSE10255 | GEO
Project description:Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improving treatment. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood, beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP resistant and sensitive ALL cells lines as well as primary leukemia samples from newly diagnosed patients. Defining ATF4 target genes in ALL cell lines using ChIP-seq revealed 25% of genes that changed expression after LASP treatment were direct targets of the ATF4 transcription factor. SLC7A11 was found to be a response gene in cell lines and patient samples as well as a direct target of ATF4. SLC7A11 was also one of only 2.4% of response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with antileukemic agent for their association with drug resistance and highlight that many response genes may not differ in their basal expression in drug resistant leukemia cells.
2022-04-15 | GSE174499 | GEO
Project description:Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improving treatment. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood, beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP resistant and sensitive ALL cells lines as well as primary leukemia samples from newly diagnosed patients. Defining ATF4 target genes in ALL cell lines using ChIP-seq revealed 25% of genes that changed expression after LASP treatment were direct targets of the ATF4 transcription factor. SLC7A11 was found to be a response gene in cell lines and patient samples as well as a direct target of ATF4. SLC7A11 was also one of only 2.4% of response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with antileukemic agent for their association with drug resistance and highlight that many response genes may not differ in their basal expression in drug resistant leukemia cells.
2022-04-15 | GSE174498 | GEO
Project description:Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improving treatment. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood, beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP resistant and sensitive ALL cells lines as well as primary leukemia samples from newly diagnosed patients. Defining ATF4 target genes in ALL cell lines using ChIP-seq revealed 25% of genes that changed expression after LASP treatment were direct targets of the ATF4 transcription factor. SLC7A11 was found to be a response gene in cell lines and patient samples as well as a direct target of ATF4. SLC7A11 was also one of only 2.4% of response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with antileukemic agent for their association with drug resistance and highlight that many response genes may not differ in their basal expression in drug resistant leukemia cells.
2022-04-15 | GSE200830 | GEO
Project description:Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50% of patients do not respond to AZA and have very poor outcomes. It is of great interest to identify predictive biomarkers for AZA responsiveness. Therefore, we searched for specific genes whose expression level was associated with response status.Using microarrays, we analyzed gene expression patterns in bone marrow CD34+ cells from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before AZA therapy. Total RNA was isolated from bone marrow CD34+ cells obtained from myelodysplasia and related neoplasms patients who underwent treatment with 5-azacytidine (AZA, Vidaza). Using Illumina Human HT-12 v. 4 microarrays, we assayed gene expression profiles in patient CD34+ cells before AZA treatment in order to collect basic data for search for markers of the prediction of therapy response.
2016-02-10 | E-GEOD-77750 | biostudies-arrayexpress
Project description:Dysregulation of kinase signaling pathways via mutations favors tumor cell survival and resistance to therapy and it is common in cancer. Here, we reveal a novel mechanism of post-translational regulation of kinase signaling and nuclear receptor activity via deubiquitination in acute leukemia. We observed that the ubiquitin specific protease 11 (USP11) is highly expressed in lymphoblastic leukemia and associates with poor prognosis in this disease. USP11 ablation inhibits leukemia growth in vitro and in vivo, sparing normal hematopoiesis and thymus development, suggesting that USP11 could be a therapeutic target in leukemia. USP11 forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK). Deubiquitination of LCK controls its activity, thereby altering T cell receptor signaling. Impairment of LCK activity leads to increased expression of the glucocorticoid receptor transcript, culminating into transcriptional activation of pro-apoptotic target genes, and sensitizes cells to glucocorticoids in primary T cell leukemia patient samples. The transcriptional activation of pro-apoptotic target genes, such as BCL2L11, is orchestrated by the deubiquitinase activity and mediated via an increase in enhancer-promoter interaction intensity. Pharmacological inhibition of USP7 or genetic knockout of USP7 in combination treatment of glucocorticoid displayed improved anti-T-ALL efficacy in vivo. Our data unveil how dysregulated deubiquitination controls signaling pathways, leading to cancer cell survival and drug non-response, and suggest novel therapeutic combinations towards targeting leukemia.
2022-02-28 | MSV000088930 | MassIVE
Project description:FMS-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in acute myeloid leukemia (AML), and is associated with a poor prognosis and high relapse rate. Gilteritinib, as a second-generation FLT3 inhibitor, is an important target drug in the treatment of FLT3-ITD AML patients, but it still faces the problems of drug resistance and reduced potency. In this study, we found that mitoxantrone-liposome can sensensitized gilteritinib and enhanced the therapeutic effect in vivo and in vitro. RNA-sequencing revealed that the combination treatment resulted in specific changes in gene expression, reduced drug resistance and the mechanism. Primary AML cells harvested from patients with FLT3-ITD AML showed a significant response to combination treatment in vitro. Our data suggest represents a novel and promising therapeutic strategy for FLT3-ITD AML patients and relapsed/refractory(R/R) AML.
2025-03-19 | GSE276384 | GEO
Project description:The metabolomics analysis of leukemia stem cells with or without drug treatment was performed using an ion chromatography mass spectrometer or a QExactive HF-X hybrid quadrupole orbitrap high-resolution mass spectrometer.
2024-07-15 | MSV000095343 | GNPS