RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins
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View abstract on PubMed
Summary
This summary is machine-generated.ZNF384-fusion (Z-fusion) genes drive B-cell acute lymphoblastic leukemia (B-ALL) by upregulating CREB5 and RGS1. RGS1 inhibits CXCL12-CXCR4 signaling, impairing cell migration and contributing to leukemogenesis.
Area Of Science
- Hematology
- Molecular Biology
- Oncology
Background
- ZNF384-fusion (Z-fusion) genes are prevalent in Japanese adult B-cell acute lymphoblastic leukemia (B-ALL), particularly in Philadelphia chromosome-negative cases.
- Z-fusion proteins, derived from the transcription factor ZNF384, exhibit enhanced transcriptional activity, but their precise role in leukemogenesis remains unclear.
Purpose Of The Study
- To elucidate the molecular mechanisms underlying Z-fusion-driven leukemogenesis.
- To identify direct transcriptional targets of Z-fusion proteins in B-ALL.
Main Methods
- Gene expression profiling (GEP) via RNA-sequencing (RNA-seq) was performed on cell lines expressing Z-fusion proteins and on clinical B-ALL samples.
- Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) was used to validate Z-fusion protein binding to candidate gene regulatory regions.
Main Results
- Six genes were consistently upregulated in both experimental models and clinical samples.
- CREB5 and RGS1 were identified as direct and common transcriptional targets of Z-fusion proteins.
- RGS1, an inhibitor of CXCL12-CXCR4 signaling crucial for B-cell development, was found to be upregulated, leading to impaired cell migration.
Conclusions
- CREB5 and RGS1 are identified as direct transcriptional targets of Z-fusion proteins.
- These findings offer new insights into the aberrant transcriptional regulation mediated by Z-fusion proteins in B-ALL pathogenesis.
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