Related Experiment Video
Updated: May 6, 2026
A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
Identification of a STAT5 target gene, Dpf3, provides novel insights in chronic lymphocytic leukemia
Marina Theodorou1, Matthaios Speletas, Antigoni Mamara
1Hematology/Oncology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Abstract:
STAT5 controls essential cellular functions and is encoded by two genes, Stat5a and Stat5b. To provide insight to the mechanisms linking hematologic malignancy to STAT5 activation/regulation of target genes, we identified STAT5 target genes and focused on Dpf3 gene, which encodes for an epigenetic factor. Dpf3 expression was induced upon IL-3 stimulation in Ba/F3 cells, while strong binding of both STAT5a and STAT5b was detected in its promoter. Reduced expression of Dpf3 was detected in Ba/F3 cells with Stat5a and Stat5b knock-down, suggesting that this gene is positively regulated by STAT5, upon IL-3 stimulation. Furthermore, this gene was significantly up-regulated in CLL patients, where DPF3 gene/protein up-regulation and strong STAT5 binding to the DPF3 promoter, correlated with increased STAT5 activation, mainly in non-malignant myeloid cells (granulocytes). Our findings provide insights in the STAT5 dependent transcriptional regulation of Dpf3, and demonstrate for the first time increased STAT5 activation in granulocytes of CLL patients. Novel routes of investigation are opened to facilitate the understanding of the role of STAT5 activation in the communication between non-malignant myeloid and malignant B-cells, and the functions of STAT5 target genes networks in CLL biology.
Insights
STAT5 (Signal Transducer and Activator of Transcription 5) regulates the Dpf3 gene, an epigenetic factor. Increased STAT5 activation was observed in granulocytes of chronic lymphocytic leukemia (CLL) patients.
Area of Science:
- * Molecular Biology
- * Cancer Biology
- * Epigenetics
Background:
- * Signal Transducer and Activator of Transcription 5 (STAT5) is crucial for cellular functions and is encoded by Stat5a and Stat5b genes.
- * STAT5 dysregulation is implicated in hematologic malignancies, but the precise mechanisms and target genes remain incompletely understood.
Purpose of the Study:
- * To elucidate the mechanisms linking STAT5 activation to hematologic malignancy by identifying STAT5 target genes.
- * To investigate the role of the epigenetic factor Dpf3 in STAT5-mediated gene regulation.
- * To explore STAT5 activation patterns in chronic lymphocytic leukemia (CLL) patients.
Main Methods:
- * Gene expression analysis in Ba/F3 cells stimulated with IL-3.
- * Chromatin immunoprecipitation (ChIP) to detect STAT5 binding to the Dpf3 promoter.
- * Analysis of Dpf3 expression and STAT5 activation in patient samples (CLL).
Main Results:
- * Dpf3 expression is induced by IL-3 and positively regulated by STAT5 in Ba/F3 cells, with STAT5 binding to its promoter.
- * Dpf3 expression was significantly upregulated in CLL patients, correlating with increased STAT5 activation, particularly in granulocytes.
- * STAT5 activation was demonstrated for the first time in granulocytes of CLL patients.
Conclusions:
- * STAT5 transcriptionally regulates the Dpf3 gene, an epigenetic factor.
- * Increased STAT5 activation in granulocytes of CLL patients suggests a role in disease biology.
- * Findings open new avenues for understanding STAT5 network functions and cell-cell communication in CLL.
More Related Videos
Related Concept Videos
01:21Lineage Commitment
01:15Differentiation of Common Myeloid Progenitor Cells