High Delta Np73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia

作者：Lucena Araujo Antonio R; Kim Haesook T; Thome Carolina; Jacomo Rafael H; Melo Raul A; Bittencourt Rosane; Pasquini Ricardo; Pagnano Katia; Gloria Ana Beatriz F; Chauffaille Maria de Lourdes; Athayde Melina; Chiattone Carlos S; Mito Ingrid; Bendlin Rodrigo; Souza Carmino; Bortolheiro Cristina; Coelho Silva Juan L; Schrier Stanley L; Tallman Martin S; Grimwade David; Ganser Arnold; Berliner Nancy; Ribeiro Raul C; Lo Coco Francesco; Lowenberg Bob; Sanz Miguel A

来源：Blood, 2015, 126(20): 2302-2306.

DOI：10.1182/blood-2015-01-623330

The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (Delta Np73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between Delta Np73 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 Delta 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 Delta Np73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the Delta Np73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.

• 出版日期2015-11-12