| First Author | Eldeeb M | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 2 | Pages | 112099 |
| PubMed ID | 36763502 | Mgi Jnum | J:348565 |
| Mgi Id | MGI:7448299 | Doi | 10.1016/j.celrep.2023.112099 |
| Citation | Eldeeb M, et al. (2023) A fetal tumor suppressor axis abrogates MLL-fusion-driven acute myeloid leukemia. Cell Rep 42(2):112099 |
| abstractText | MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. Mechanistically, LIN28B directly binds to MYBBP1A mRNA, resulting in elevated protein levels of this MYB co-repressor. Functionally, overexpression of MYBBP1A phenocopies the tumor-suppressor effects of LIN28B, while its perturbation omits it. Thereby, we propose that developmentally restricted expression of LIN28B provides a layer of protection against MYB-dependent AML. |
