High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia Journal Article
| Authors: | Lucena-Araujo, A. R.; Kim, H. T.; Thomé, C.; Jacomo, R. H.; Melo, R. A.; Bittencourt, R.; Pasquini, R.; Pagnano, K.; Glória, A. B. F.; de Lourdes Chauffaille, M.; Athayde, M.; Chiattone, C. S.; Mito, I.; Bendlin, R.; Souza, C.; Bortolheiro, C.; Coelho-Silva, J. L.; Schrier, S. L.; Tallman, M. S.; Grimwade, D.; Ganser, A.; Berliner, N.; Ribeiro, R. C.; Lo-Coco, F.; Löwenberg, B.; Sanz, M. A.; Rego, E. M. |
| Article Title: | High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia |
| Abstract: | The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (DNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between DNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ?Np73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ?Np73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P 5 .0035). Our data support the hypothesis that the ?Np73/TAp73 ratio is an important determinant of clinical responsein APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells. © 2015 by The American Society of Hematology. |
| Keywords: | adolescent; adult; cancer chemotherapy; child; controlled study; treatment response; aged; survival rate; unclassified drug; major clinical study; overall survival; histopathology; cancer patient; disease free survival; gene expression; transcription factor; high risk patient; confidence interval; rna; tumor suppressor gene; proportional hazards model; promyelocytic leukemia; hazard ratio; anthracycline; tumor suppressor protein; retinoic acid; predictive value; receiver operating characteristic; diagnostic test accuracy study; cancer prognosis; human; male; female; priority journal; article; np73 protein; tap73 protein |
| Journal Title: | Blood |
| Volume: | 126 |
| Issue: | 20 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2015-11-12 |
| Start Page: | 2302 |
| End Page: | 2306 |
| Language: | English |
| DOI: | 10.1182/blood-2015-01-623330 |
| PROVIDER: | scopus |
| PUBMED: | 26429976 |
| PMCID: | PMC4760128 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 7 January 2016 -- 2302 -- Source: Scopus |
