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Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines

ABSTRACT: Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines

PROVIDER: PRJNA1202113 | ENA |

REPOSITORIES: ENA

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Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [RNA-seq]

Project description:Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [RNA-seq]

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Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [Bisulfite-Seq]

Project description:Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [Bisulfite-Seq]

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Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [RNA-seq]

Project description:Background Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low. In this study, we investigate the effects of hypoxia on HMA responses in AML cells. Results AML cell lines (MOLM-13, MV-4-11, HL-60) were treated with DAC (100nM) or AZA (500-2000nM) in normoxic (21% O2) and hypoxic (1% O2) conditions. Hypoxia significantly reduced AML cell growth and colony-forming capacity across all cell lines, with no additional effects observed upon HMA treatment. Hypoxia had no impact on the extent of DNA hypomethylation induced by DAC treatment, but limited AZA-induced loss of methylation from the genome. Transcriptional responses to HMA treatment were also altered, with HMAs failing to up-regulate antigen presentation pathways in hypoxia. In particular, cell surface expression of the MHC class II receptor, HLA-DR, was increased by DAC treatment in normoxia, but not hypoxia. Conclusion Our results suggest that HMA-induced antigen presentation may be impaired by hypoxia. This study highlights the need to consider microenvironmental factors when designing co-treatment strategies to improve HMA therapeutic efficacy.

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Transcriptome analysis of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs in aplastic anemia patients

Project description:HLA-DR-lacking HSPCs [HLA-DR(-) HSPCs] were detected in aplastic anemia (AA) patients with HLA-DR15. HLA-DR(-) HSPCs may evade the attack by CD4+ T-cells recognizing the autoantigen presented by HLA-DR15. The goal of this study is to clarify the immune escape mechanisms from antigen-specific T-cells by comparing the trranscriptome profile of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs.

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Project description:Myeloid-derived suppressor cells (MDSC) is a heterogeneous population of cells that can negatively regulate T-cell function. As opposed to murine MDSC, which are characterized as Gr-1+CD11b+ cells, human MDSC are not so clearly defined due to lack of specific markers. Our lab has previously identified a new subset of MDSC as CD14+HLA-DR-neg/low cells from PBMC. CD14+HLA-DR-neg/low MDSC not only suppress proliferation and IFN-gamma secretion of autologous T cells, but also induce CD25+Foxp3+ regulatory T cells that are suppressive in vitro, whereas the counterpart CD14+HLA-DR-high monocytes don’t have the effect. In this study, we compare the immune-related gene expression between CD14+HLA-DR-neg/low MDSC and CD14+HLA-DR-high monocytes to better characterize the difference between these two populations and to find new potential specific marker for human MDSC. PBMC were isolated from fresh blood healthy donor by density centrifugation. CD14+ cells were isolated by AutoMACS CD14 microbeads using a AutoMACS (Miltenyi), and then stained with CD14 and HLA-DR antibodies. MDSC and monocytes control cells were sorted as CD14+ HLA-DR-neg/low and CD14+HLA-DR-high cells respectively. The sorted two populations were immediately frozen in liquid nitrogen and shipped to the company on dry ice for RNA isolation and further microarray.

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Transcriptome analysis of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs in aplastic anemia patients

Project description:Transcriptome analysis of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs in aplastic anemia patients

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Project description:This SuperSeries is composed of the SubSeries listed below.

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