| First Author | Tonc E | Year | 2021 |
| Journal | Blood | Volume | 138 |
| Issue | 24 | Pages | 2526-2538 |
| PubMed ID | 34283887 | Mgi Jnum | J:322736 |
| Mgi Id | MGI:7260024 | Doi | 10.1182/blood.2021011711 |
| Citation | Tonc E, et al. (2021) Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes. Blood 138(24):2526-2538 |
| abstractText | The proliferative burst of B lymphocytes is essential for antigen receptor repertoire diversification during the development and selective expansion of antigen-specific clones during immune responses. High proliferative activity inevitably promotes oncogenesis, the risk of which is further elevated in B lymphocytes by endogenous gene rearrangement and somatic mutations. However, B-cell-derived cancers are rare, perhaps owing to putative intrinsic tumor-suppressive mechanisms. We show that c-MYC facilitates B-cell proliferation as a protumorigenic driver and unexpectedly coengages counteracting tumor suppression through its downstream factor TFAP4. TFAP4 is mutated in human lymphoid malignancies, particularly in >10% of Burkitt lymphomas, and reduced TFAP4 expression was associated with poor survival of patients with MYC-high B-cell acute lymphoblastic leukemia. In mice, insufficient TFAP4 expression accelerated c-MYC-driven transformation of B cells. Mechanistically, c-MYC suppresses the stemness of developing B cells by inducing TFAP4 and restricting self-renewal of proliferating B cells. Thus, the pursuant transcription factor cascade functions as a tumor suppressor module that safeguards against the transformation of developing B cells. |
