| First Author | Pereira-Martins DA | Year | 2026 |
| Journal | Cell Rep Med | Volume | 7 |
| Issue | 1 | Pages | 102540 |
| PubMed ID | 41512877 | Mgi Jnum | J:378413 |
| Mgi Id | MGI:8281370 | Doi | 10.1016/j.xcrm.2025.102540 |
| Citation | Pereira-Martins DA, et al. (2026) DeltaNp73 isoform defines a TP53-mutant-like poor-risk subgroup of acute myeloid leukemia. Cell Rep Med 7(1):102540 |
| abstractText | Among acute myeloid leukemia (AML) patients, a subgroup remains notoriously refractory to current treatment options, with underlying mechanisms poorly understood. Here, using a multi-omics approach, we reveal that this resistant patient subgroup is characterized by high expression of the oncogenic TP73 isoform DeltaNp73, exhibiting similarly poor outcomes as TP53-mutant AML. DeltaNp73, which lacks a transcriptional activation domain but retains chromatin-binding properties, competes with TP53 for specific gene targets, thereby downregulating TP53 signaling. We demonstrate that the transcription factor CEBPA controls DeltaNp73 expression in AML cells by binding to an intragenic enhancer region. Genetic or pharmacological inhibition of the transcriptional activity of CEBPA with guanfacine reduces DeltaNp73 levels and restores drug sensitivity involving ferroptosis-mediated cell death, acting synergistically with venetoclax. Our study sheds light on a previously undercharacterized poor-risk subgroup of AML, which may support patient stratification and inform treatment considerations. |
