| First Author | Weng H | Year | 2022 |
| Journal | Cancer Cell | Volume | 40 |
| Issue | 12 | Pages | 1566-1582.e10 |
| PubMed ID | 36306790 | Mgi Jnum | J:370317 |
| Mgi Id | MGI:7413780 | Doi | 10.1016/j.ccell.2022.10.004 |
| Citation | Weng H, et al. (2022) The m(6)A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. Cancer Cell 40(12):1566-1582.e10 |
| abstractText | N(6)-Methyladenosine (m(6)A) modification and its modulators play critical roles and show promise as therapeutic targets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recently reported as an m(6)A binding protein that enhances mRNA stability and translation. However, its function in AML remains largely elusive. Here we report the oncogenic role and the therapeutic targeting of IGF2BP2 in AML. High expression of IGF2BP2 is observed in AML and associates with unfavorable prognosis. IGF2BP2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating expression of critical targets (e.g., MYC, GPT2, and SLC1A5) in the glutamine metabolism pathways in an m(6)A-dependent manner. Inhibiting IGF2BP2 with our recently identified small-molecule compound (CWI1-2) shows promising anti-leukemia effects in vitro and in vivo. Collectively, our results reveal a role of IGF2BP2 and m(6)A modification in amino acid metabolism and highlight the potential of targeting IGF2BP2 as a promising therapeutic strategy in AML. |
