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Details for article 22 of 23 found articles
| Title: |
The identification and characterization of a STAT5 gene signature in hematologic malignancies |
| Author: |
Sonkin, Dmitriy Palmer, Michael Rong, Xianhui Horrigan, Kim Regnier, Catherine H. Fanton, Christie Holash, Jocelyn Pinzon-Ortiz, Maria Squires, Matthew Sirulnik, Andres Radimerski, Thomas Schlegel, Robert Morrissey, Michael Cao, Z. Alexander |
| Appeared in: |
Disease markers. Section A, Cancer biomarkers |
| Paging: | Volume 15 (2014) nr. 1 pages 79-87 |
| Year: |
2014-12-10 |
| Contents: |
BACKGROUND: The JAK-STAT pathway is an important signaling pathway downstream of multiple cytokine and growth factor receptors. Dysregulated JAK-STAT signaling has been implicated in the pathogenesis of multiple human malignancies. OBJECTIVE: Given this pivotal role of JAK-STAT dysregulation, it is important to identify patients with an overactive JAK-STAT pathway for possible treatment with JAK inhibitors. METHODS: We developed a gene signature assay to detect overactive JAK-STAT signaling. The cancer cell line encyclopedia and associated gene-expression data were used to correlate the activation status of STAT5 with the induction of a set of STAT5 target genes. RESULTS: Four target genes were identified (PIM1, CISH, SOCS2, and ID1), the expression of which correlated significantly with pSTAT5 status in 40 hematologic tumor cell lines. In pSTAT5-positive models, the expression of the gene signature genes decreased following ruxolitinib treatment, which corresponded to pSTAT5 downmodulation. In pSTAT5-negative cell lines, neither pSTAT5 modulation nor a change in signature gene expression was observed following ruxolitinib treatment. CONCLUSIONS: The gene signature can potentially be used to stratify or enrich for patient populations with activated JAK-STAT5 signaling that might benefit from treatments targeting JAK-STAT signaling. Furthermore, the 4-gene signature is a predictor of the pharmacodynamic effects of ruxolitinib. |
| Publisher: |
IOS Press |
| Source file: |
Elektronische Wetenschappelijke Tijdschriften |
Details for article 22 of 23 found articles
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