| First Author | Volanakis EJ | Year | 2013 |
| Journal | Exp Hematol | Volume | 41 |
| Issue | 4 | Pages | 377-86 |
| PubMed ID | 23178376 | Mgi Jnum | J:214047 |
| Mgi Id | MGI:5587902 | Doi | 10.1016/j.exphem.2012.11.006 |
| Citation | Volanakis EJ, et al. (2013) Epigenetic regulation of the Ink4a-Arf (Cdkn2a) tumor suppressor locus in the initiation and progression of Notch1-driven T cell acute lymphoblastic leukemia. Exp Hematol 41(4):377-86 |
| abstractText | Activating mutations of NOTCH1 and deletion of the INK4A-ARF (CDKN2A) tumor suppressor locus are two of the most frequent genetic alterations in T cell acute lymphoblastic leukemia (T-ALL). In a murine model of T-ALL induced by the intracellular domain of Notch1 (ICN1), the genetic interaction between ICN1 signaling and Arf inactivation is developmentally stage-specific, with a more pronounced requirement for Arf deletion in thymocytes than in bone marrow precursors targeted for transformation. In the thymus, the target cell for transformation is a CD4 and CD8 double-negative progenitor that undergoes T cell receptor beta-chain rearrangement, a cell type in which polycomb silencing of Ink4a-Arf is normally requisite. Epigenetic remodeling during tumor progression licenses Arf as a tumor suppressor and in turn provides the selective pressure for Ink4a-Arf deletion in clonal T-ALLs that emerge. |
