The identification and characterization of a STAT5 gene signature in hematologic malignancies.
Cancer Biomark
; 15(1): 79-87, 2015.
Article
in En
| MEDLINE
| ID: mdl-25524945
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematologic Neoplasms
/
STAT5 Transcription Factor
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Biomark
Journal subject:
BIOQUIMICA
/
NEOPLASIAS
Year:
2015
Document type:
Article
Affiliation country:
United States