Dataset Information

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

ABSTRACT:

Background

Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established role in promoting apoptosis in MDS. Therefore, TNFα has the potential to be a valuable biomarker for predicting the progression of cytopenia in MDS. This study aims to establish the role of TNFα exposure in triggering apoptosis through caspase-3 activity in CD34+, CD33+, and CD41 + cells in MDS.

Methods

This study is an in vitro comparative experimental research. Bone marrow mononuclear cells were isolated as the source of hematopoietic progenitor cells. Subsequently, CD34+, CD33+, and CD41 + cells were exposed to rhTNFα, and the caspase-3 activity was measured using flowcytometry.

Results

In MDS CD33 + and CD41 + caspase-3 activity of rhTNFα exposed cells was significantly higher than without exposed cells. The opposite result was found in CD34 + cells, where the caspase-3 activity without rhTNFα exposed cells was significantly higher than rhTNFα exposed cells.

Conclusion

rhTNFα exposure led to an elevation in caspase-3 activity in MDS progenitor cells, especially in those that had differentiated into myeloid cell CD33 + and megakaryocyte cell CD41+, as opposed to the early progenitor cells CD34+.

SUBMITTER: Iriani A

PROVIDER: S-EPMC10662645 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

Iriani Anggraini A Rachman Andhika A Setiabudy Rahayuningsih D RD Kresno Siti B SB Sudoyo Aru W AW Arief Mansyur M Harahap Alida R AR Fatina Marsya Kaila MK

BMC molecular and cell biology 20231121 1

<h4>Background</h4>Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established role in promoting apoptosis in MDS. Therefore, TNFα has the potential to be a valuable biomarker for predicting the progression of cytopenia in MDS. This study aims to establish the role of TNFα exposure in triggering apoptosis through caspase-3 activity in CD34+, CD33+, ...[more]

PMID: 37990142

Similar Datasets

Project description:ObjectiveThis study aims to investigate and analyze the differentially expressed genes (DEGs) in CD34 + hematopoietic stem cells (HSCs) from patients with myelodysplastic syndromes (MDS) through bioinformatics analysis, with the ultimate goal of uncovering the potential molecular mechanisms underlying pathogenesis of MDS. The findings of this study are expected to provide novel insights into clinical treatment strategies for MDS.MethodsInitially, we downloaded three datasets, GSE81173, GSE4619, and GSE58831, from the public Gene Expression Omnibus (GEO) database as our training sets, and selected the GSE19429 dataset as the validation set. To ensure data consistency and comparability, we standardized the training sets and removed batch effects using the ComBat algorithm, thereby integrating them into a unified gene expression dataset. Subsequently, we conducted differential expression analysis to identify genes with significant changes in expression levels across different disease states. In order to enhance prediction accuracy, we incorporated six common predictive models and trained them based on the filtered differential gene expression dataset. After comprehensive evaluation, we ultimately selected three algorithms-Lasso regression, random forest, and support vector machine (SVM)-as our core predictive models. To more precisely pinpoint genes closely related to disease characteristics, we utilized the aforementioned three machine learning methods for prediction and took the intersection of these prediction results, yielding a more robust list of genes associated with disease features. Following this, we conducted in-depth analysis of these key genes in the training set and validated the results independently using the GSE19429 dataset. Furthermore, we performed differential analysis of gene groups, co-expression analysis, and enrichment analysis to delve deeper into the mechanisms underlying the roles of these genes in disease initiation and progression. Through these analyses, we aim to provide new insights and foundations for disease diagnosis and treatment. Figure illustrates the data preprocessing and analysis workflow of this study.ResultsOur analysis of differentially expressed genes (DEGs) in CD34+ hematopoietic stem cells (HSCs) from patients with myelodysplastic syndromes (MDS) revealed significant differences in gene expression patterns compared to the control group (individuals without MDS). Specifically, the expression levels of two key genes, IRF4 and ELANE, were notably downregulated in CD34+ HSCs of MDS patients, indicating their downregulatory roles in the pathological process of MDS.ConclusionThis study sheds light on the potential molecular mechanisms underlying MDS, with a particular focus on the pivotal roles of IRF4 and ELANE as key pathogenic genes. Our findings provide a novel perspective for understanding the complexity of MDS and exploring therapeutic strategies. They may also guide the development of precise and effective treatments, such as targeted interventions directed against these genes.

Dataset Information

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

Background

Methods

Results

Conclusion

Publications

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

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