| First Author | Richart L | Year | 2020 |
| Journal | Oncogene | Volume | 39 |
| Issue | 25 | Pages | 4884-4895 |
| PubMed ID | 32451433 | Mgi Jnum | J:290522 |
| Mgi Id | MGI:6441245 | Doi | 10.1038/s41388-020-1331-3 |
| Citation | Richart L, et al. (2020) Bptf determines oncogenic addiction in aggressive B-cell lymphomas. Oncogene 39(25):4884-4895 |
| abstractText | Chromatin remodeling factors contribute to establish aberrant gene expression programs in cancer cells and therefore represent valuable targets for therapeutic intervention. BPTF (Bromodomain PhD Transcription Factor), a core subunit of the nucleosome remodeling factor (NURF), modulates c-MYC oncogenic activity in pancreatic cancer. Here, we analyze the role of BPTF in c-MYC-driven B-cell lymphomagenesis using the Emu-Myc transgenic mouse model of aggressive B-cell lymphoma. We find that BPTF is required for normal B-cell differentiation without evidence of haploinsufficiency. In contrast, deletion of one Bptf allele is sufficient to delay lymphomagenesis in Emu-Myc mice. Tumors arising in a Bptf heterozygous background display decreased c-MYC levels and pathway activity, together with increased activation of the NF-kappaB pathway, a molecular signature characteristic of human diffuse large B-cell lymphoma (DLBCL). In human B-cell lymphoma samples, we find a strong correlation between BPTF and c-MYC mRNA and protein levels, together with an anti-correlation between BPTF and NF-kappaB pathway activity. Our results indicate that BPTF is a relevant therapeutic target in B-cell lymphomas and that, upon its inhibition, cells acquire distinct oncogenic dependencies. |
