Expression profiling with RNA-seq between mouse AML cells with or without chemotherapy
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ABSTRACT:
PROVIDER: PRJNA678444 | ENA |
REPOSITORIES: ENA
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Project description:We reported the expression profiling between mouse AML cells with or without chemotherapy. For this purpose, mouse AML cells were harvested from mice treated with or without chemotherapy drugs on day 7. Gene expression analysis of AML cells with or without chemotherapy identified clearly distinguishable transcriptomic profiles. GO analysis revealed that gene alterations after chemotherapy were related to immune response, RNA biology and several metabolomic processes. mTORC1 signal-related GSEA signatures were also enriched in AML cells after chemotherapy including those of stemness and impaired differentiation.
2020-11-29 | GSE161490 | GEO
Project description:Nucleophosmin mutated AML (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Since miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (ageM-bM-^IM-%60 years) AML patients. Loss and gain of function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML. Pretreatment miRNA expression was analyzed in 54 de novo adult AML patients obtained from the MD Anderson Cancer Center Leukemia Tissue Bank (LTB) using the Ohio State University (OSU) miRNA microarray (ver.3).
2014-05-01 | E-GEOD-55519 | biostudies-arrayexpress
Project description:Nucleophosmin mutated AML (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Since miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (age≥60 years) AML patients. Loss and gain of function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML.
2014-05-01 | GSE55519 | GEO
Project description:The paper describes a model of acute myeloid leukaemia.
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This model is described in the article:
Optimal control of acute myeloid leukaemia
Jesse A. Sharp, Alexander P Browning, Tarunendu Mapder, Kevin Burrage, Matthew J Simpson
Journal of Theoretical Biology 470 (2019) 30–42
Abstract:
Acute myeloid leukaemia (AML) is a blood cancer affecting haematopoietic stem cells. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corre- sponding to a range of objectives and parameter choices. Through example calculations, we provide a practical approach to applying optimal control using Pontryagin’s Maximum Principle. In particular, we describe and explore factors that have a profound influence on numerical convergence. We find that the convergence behaviour is sensitive to the method of control updating, the nature of the control, and to the relative weighting of terms in the objective function. All codes we use to implement optimal control are made available.
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2024-09-02 | BIOMD0000000798 | BioModels
Project description:Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multi-omics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1-S34F and U2AF1-Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA-seq. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway.
2024-02-20 | GSE256127 | GEO
Project description:Transcriptional profiles of highly purified (≥ 98%) PB CD4+ or CD8+ T cells at early lymphocyte recovery (ELR) from newly diagnosed AML patients, who were treated with standard induction chemotherapy plus pomalidomide were compared to age-matched AML controls, who received standard induction chemotherapy only.
2022-05-05 | GSE130753 | GEO
Project description:We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range anticancer effects in a variety of human cancers. Here, using acute myeloid leukemia as a model, we reported a less toxic analog of DZNep, named D9, that is shown to be efficacious in both cell lines and patient samples of AML. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and is implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival and associated gene expression when combined with chemotherapy. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy. We found D9 treatment depleted chemotherapy-induced LSC. We next sought to characterize the molecular changes induce by the chemotherapy that is antagonized by D9. To do this, TF-1a cells before and after Ara-C or ADR treatment or co-treated with D9 were harvested for RNA isolation and genome-wide transcription profilling.
2015-12-31 | E-GEOD-59625 | biostudies-arrayexpress
Project description:Comparing between plasma cytokine proteins on AML patients with or without aGVHD Comparing between plasma cytokine proteins on AML patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation, Day+14
2022-06-11 | GSE205842 | GEO
Project description:To clarify the global gene expression alteration in primary CD34+ AML cells after BCAA metabolism inhibition, CD34+ AML cells were treated with or without gabapentin in vitro. After 9-12 hours of culture with or without gabapentin, FACS-purified CD34+ AML cells were subjected to transcriptome analysis.
2019-06-01 | GSE127181 | GEO
Project description:We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range anticancer effects in a variety of human cancers. Here, using acute myeloid leukemia as a model, we reported a less toxic analog of DZNep, named D9, that is shown to be efficacious in both cell lines and patient samples of AML. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and is implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival and associated gene expression when combined with chemotherapy. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy.
2015-12-31 | GSE59625 | GEO