| First Author | Sochalska M | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 15 | Pages | 2066-2073 |
| PubMed ID | 27694901 | Mgi Jnum | J:241093 |
| Mgi Id | MGI:5897720 | Doi | 10.1038/onc.2016.362 |
| Citation | Sochalska M, et al. (2017) MYC selects against reduced BCL2A1/A1 protein expression during B cell lymphomagenesis. Oncogene 36(15):2066-2073 |
| abstractText | Rearrangements of MYC or ABL proto-oncogenes lead to deregulated expression of key-regulators of cell cycle and cell survival, thereby constituting important drivers of blood cancer. Members of the BCL-2 family of apoptosis regulators contribute to oncogenic transformation downstream of these oncogenes, but the role of anti-apoptotic BCL2A1/A1 in transformation and drug resistance caused by deregulation of these oncogenes remains enigmatic. Here we analyzed the role of A1 in MYC as well as ABL kinase-driven blood cancer in mice, employing in vivo RNAi. We report that overexpression of either oncogene leads to a significant increase in A1 protein levels in otherwise A1-negative B cell progenitors, indicating a key role downstream of these oncogenes to secure survival during transformation. Knockdown of A1 by RNAi, however, did not impact on tumor latency in v-Abl-driven pre-B-ALL. In contrast, A1 knockdown in premalignant Emu-MYC mice caused a significant reduction of transgenic pre-B cells without impacting on tumor latency as the emerging lymphomas escaped silencing of A1 expression. These findings identify A1 as a MYC target that can be induced prematurely during B cell development to aid expansion of otherwise cell-death-prone MYC transgenic pre-B cells. Hence, A1 should be considered as a putative drug target in MYC-driven blood cancer. |
