| First Author | Vanden Bempt M | Year | 2018 |
| Journal | Cancer Cell | Volume | 34 |
| Issue | 2 | Pages | 271-285.e7 |
| PubMed ID | 30107177 | Mgi Jnum | J:264234 |
| Mgi Id | MGI:6195949 | Doi | 10.1016/j.ccell.2018.07.007 |
| Citation | Vanden Bempt M, et al. (2018) Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214-ABL1/TLX1-Positive T Cell Acute Lymphoblastic Leukemia. Cancer Cell 34(2):271-285.e7 |
| abstractText | The NUP214-ABL1 fusion is a constitutively activated tyrosine kinase that is significantly associated with overexpression of the TLX1 and TLX3 transcription factors in T cell acute lymphoblastic leukemia (T-ALL). Here we show that NUP214-ABL1 cooperates with TLX1 in driving T-ALL development using a transgenic mouse model and human T-ALL cells. Using integrated ChIP-sequencing, ATAC-sequencing, and RNA-sequencing data, we demonstrate that TLX1 and STAT5, the downstream effector of NUP214-ABL1, co-bind poised enhancer regions, and cooperatively activate the expression of key proto-oncogenes such as MYC and BCL2. Inhibition of STAT5, downregulation of TLX1 or MYC, or interference with enhancer function through BET-inhibitor treatment leads to reduction of target gene expression and induction of leukemia cell death. |
