| First Author | Nucera S | Year | 2016 |
| Journal | Cancer Cell | Volume | 29 |
| Issue | 6 | Pages | 905-921 |
| PubMed ID | 27300437 | Mgi Jnum | J:232327 |
| Mgi Id | MGI:5776623 | Doi | 10.1016/j.ccell.2016.05.007 |
| Citation | Nucera S, et al. (2016) miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia. Cancer Cell 29(6):905-21 |
| abstractText | MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden. |
