| First Author | Steinman RA | Year | 2013 |
| Journal | Int J Cancer | Volume | 132 |
| Issue | 8 | Pages | 1741-50 |
| PubMed ID | 22987615 | Mgi Jnum | J:315224 |
| Mgi Id | MGI:6829829 | Doi | 10.1002/ijc.27851 |
| Citation | Steinman RA, et al. (2013) Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice. Int J Cancer 132(8):1741-50 |
| abstractText | Patients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase inhibitors (TKIs) of the Bcr-Abl oncoprotein. However, intolerance and resistance to these agents remains a challenge, and TKIs are unable to eradicate rare leukemia-initiating cells. Leukemia treatment would benefit from a better understanding of molecular signals that are necessary for the survival of leukemia-initiating cells but dispensable for normal hematopoietic stem cells. Leukemia-initiating cells in CML can arise from myeloid progenitor cells, a population that we have reported in normal hematopoiesis to depend on the RNA-editing enzyme adenosine deaminase acting on RNA-1 (ADAR1). We now report that Bcr-Abl transformed leukemic cells were ADAR1-dependent in a conditional ADAR1 knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and preferentially depleted primitive Lin-Sca+Kit+ (LSK) leukemic cells but not LSK cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the peripheral white blood count, eliminating leukemic cells as assessed by PCR. These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and indicate that ADAR1 may comprise a new molecular target for CML-directed therapeutics. |
