Transcriptomics

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Gene expression profile of Baf3 cells overexpressing TPR-FGFR1 fusion gene


ABSTRACT: Nowadays, fibroblast growth factor receptor 1 (FGFR1) inhibitors are considered as an effective kinase inhibitor for 8p11 myeloproliferative syndrome (EMS) treatment. However, targeting FGFR1 alone may not be sufficient in EMS patients with TPR-FGFR1 rearrangement. In this study, we established TPR FGFR1 expressing Baf3 cells and performed RNA-Seq analysis. RNA-Seq analysis revealed that genes associated with TPR-FGFR1 expression mainly participated in the epidermal growth factor receptor (EGFR) pathway (|FC| > 1.80, P < 0.05). Gene set enrichment analysis (GSEA) identified significant enrichment in the PI3K/AKT pathways. We found that EGFR is another activation pathway for AKT in TPR-FGFR1-expressing Baf3 cells. Moreover, we found that treatment with FGFR1 inhibitors alone could completely inhibit FGFR1 phosphorylation, but could not completely inhibit AKT, which is the downstream molecule of FGFR1. Compared to FGFR1 inhibitors alone, co-treatment with PD-166866 (FGFR1 inhibitor) and MK-2206 (AKT inhibitor) could simultaneously inhibit the phosphorylation of FGFR1 and AKT. In addition, FACS results indicated that the combination therapy of PD-168866 and MK-2206 significantly increased the rate of cells apoptosis than monotherapy of PD-166866 (P < 0.0001). Collectively, the data obtained in the present study provides strong evidence for dual targeting therapy of FGFR1 and AKT in EMS patients with TPR-FGFR1 rearrangement, offering a new direction for EMS treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE272597 | GEO | 2024/07/21

REPOSITORIES: GEO

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