Expression profiling of CD4+and CD8+ T cells in peripheral blood (PB) of AML patients who were treated with induction chemotherapy plus pomalidomide
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PROVIDER: PRJNA541283 | ENA |
REPOSITORIES: ENA
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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:1) Transcriptional profiles of highly purified (≥ 98%) PB CD8+ T-cells from newly diagnosed AML patients (pre-treatment) were compared to age-matched healthy controls and transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment and upon recovery following induction chemotherapy (paired samples). 2) Transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment (PRE) and upon recovery following induction chemotherapy (POST) (paired samples).
2018-12-26 | GSE109179 | GEO
Project description:Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients remain refractory or relapse upon standard chemotherapy based on nucleoside analogs plus anthracyclines. The crosstalk between AML cells and the bone marrow (BM) stroma is a major mechanism underlying therapy resistance in AML. Lenalidomide and pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess pleiotropic anti-leukemic properties including potent immune-modulating effects and are commonly used in hematological malignances associated with intrinsic dysfunctional BM such as myelodysplastic syndromes and multiple myeloma. Whether IMiDs may improve the efficacy of current standard treatment in AML remains understudied. Here, we have exploited in vitro and in vivo preclinical AML models to analyze whether IMiDs potentiate the efficacy of AraC/Iradubicin (standard AML chemotherapy) by interfering with the BM stroma-mediated chemoresistance. We report that lenalidomide and pomalidomide have cytotoxic effects on neither AML cells nor BM-MSCs, but they increase the immunosuppressive/immunomodulatory properties of BM-MSCs. When combined with AraC and Idarubicin, IMiDs fail to circumvent BM stroma-mediated resistance of AML cells in vitro and in vivo but induce robust extramedullary mobilization of AML cells. When administered as a single agent, lenalidomide highly mobilizes AML cells, but not healthy CD34+ cells, to peripheral blood (PB) likely through specific downregulation of CXCR4 in AML blasts. Global gene expression profiling supports a migratory/mobilization gene signature in lenalidomide-treated AML blasts but not in CD34+ cells. Collectively, IMiDs mobilize AML blasts to PB through downregulation of CXCR4 but do not improve AraC/Idarubicin activity in a preclinical model of AML.
2019-05-17 | GSE106748 | GEO
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:Therapy resistance represents a major clinical challenge in acute myeloid leukemia (AML). Here we define a “MitoScore” signature that identifies high mitochondrial oxidative phosphorylation (OxPHOS) in vivo and in AML patients. Primary AML cells with cytarabine (AraC) resistance and high MitoScore relied on mitochondrial Bcl2 and were highly sensitive to venetoclax (VEN) plus AraC (but not to VEN plus azacytidine, AZA). Single-cell transcriptomics of VEN+AraC-residual cell populations revealed adaptive resistance associated with changes in OxPHOS, electron transport chain complex (ETC) and the TP53 pathway.
2021-11-12 | GSE183329 | 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:Genome wide CRISPR screen in AML chemotherapy resistance.
| PRJNA986910 | ENA
Project description:U2AF1 mutations confer resistance to chemotherapy in AML
| PRJNA1078301 | ENA
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