| First Author | Tran TM | Year | 2022 |
| Journal | Leukemia | Volume | 36 |
| Issue | 1 | Pages | 68-79 |
| PubMed ID | 34321607 | Mgi Jnum | J:327031 |
| Mgi Id | MGI:6852653 | Doi | 10.1038/s41375-021-01346-7 |
| Citation | Tran TM, et al. (2022) The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis. Leukemia 36(1):68-79 |
| abstractText | Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia. |
