| First Author | Tsuzuki S | Year | 2013 |
| Journal | Stem Cells | Volume | 31 |
| Issue | 2 | Pages | 236-47 |
| PubMed ID | 23135987 | Mgi Jnum | J:318020 |
| Mgi Id | MGI:6858634 | Doi | 10.1002/stem.1277 |
| Citation | Tsuzuki S, et al. (2013) TEL (ETV6)-AML1 (RUNX1) initiates self-renewing fetal pro-B cells in association with a transcriptional program shared with embryonic stem cells in mice. Stem Cells 31(2):236-47 |
| abstractText | The initial steps involved in the pathogenesis of acute leukemia are poorly understood. The TEL-AML1 fusion gene usually arises before birth, producing a persistent and covert preleukemic clone that may convert to precursor B cell leukemia following the accumulation of secondary genetic "hits." Here, we show that TEL-AML1 can induce persistent self-renewing pro-B cells in mice. TEL-AML1+ cells nevertheless differentiate terminally in the long term, providing a "window" period that may allow secondary genetic hits to accumulate and lead to leukemia. TEL-AML1-mediated self-renewal is associated with a transcriptional program shared with embryonic stem cells (ESCs), within which Mybl2, Tgif2, Pim2, and Hmgb3 are critical and sufficient components to establish self-renewing pro-B cells. We further show that TEL-AML1 increases the number of leukemia-initiating cells that are generated in collaboration with additional genetic hits, thus providing an overall basis for the development of novel therapeutic and preventive measures targeting the TEL-AML1-associated transcriptional program. |
