SETBP1 expression

Clinically, a striking difference in disease aggressiveness was noted, with SETBP1-mutated patients showing a much worse clinical course. As opposite to myelodysplastic/myeloproliferative neoplasms, where SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in three TN-PMF patients from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.

This study provides insight into the landscape of SETBP1 expression and TF activity across 31 non-diseased human tissues and reveals tissue-specific expression and activity of SETBP1 and its targets. In conjunction with the web application we constructed, our framework enables researchers to generate hypotheses related to the role tissue backgrounds play with respect to gene expression and TF activity in different disease contexts.

The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.

GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression. SETBP1 may play a dual role in GC progression.

The clinical significance was established by the association of TRIM29 and SETBP1 expression with clinicopathological features in OC samples. The SETBP1/SET/PP2A axis driven by TRIM29 via transcription factor VEZF1 is at least one of the primary mechanisms underlying TRIM29 maintenance of the CSC-like characteristics in OC.

To identify genetic vulnerabilities of these AMLs, we performed genome-wide CRISPR-Cas9 screening in Flt3ITD/+/Setbp1IM+ AMLs and identified potential therapeutic targets, including Kdm1a, Brd3, Ezh2, and Hmgcr. Our study gives new insights into epigenetic pathways that can drive AMLs lacking class-defining mutations and proposes therapeutic approaches against such cases.