| First Author | Katerndahl CDS | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 6 | Pages | 694-704 |
| PubMed ID | 28369050 | Mgi Jnum | J:260614 |
| Mgi Id | MGI:6142532 | Doi | 10.1038/ni.3716 |
| Citation | Katerndahl CDS, et al. (2017) Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival. Nat Immunol 18(6):694-704 |
| abstractText | The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCbeta, NF-kappaB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-kappaB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4 and IKAROS. Patients with a high ratio of active STAT5 to NF-kappaB or IKAROS had more-aggressive disease. Our studies indicate that an imbalance of two opposing transcriptional programs drives B-ALL and suggest that restoring the balance of these pathways might inhibit B-ALL. |
