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

Fecha de publicación: 12/11/2015

Autores de IIS La Fe

Miguel Ángel Sanz Alonso

Autor

Participantes ajenos a IIS La Fe

Lucena-Araujo AR
Kim HT
Thomé C
Jacomo RH
Melo RA
Bittencourt R
Pasquini R
Pagnano K
Glória AB
Chauffaille Mde L
Athayde M
Chiattone CS
Mito I
Bendlin R
Souza C
Bortolheiro C
Coelho-Silva JL
Schrier SL
Tallman MS
Grimwade D
Ganser A
Berliner N
Ribeiro RC
Lo-Coco F
Löwenberg B
Rego EM

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 0006-4971, 1528-0020
Tipo:: Article
Páginas:: 2302-2306
DOI:: 10.1182/blood-2015-01-623330
Factor de Impacto:: 6,353 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Lucena-Araujo AR:: Department of Internal Medicine, Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of São Paulo, Ribeirao Preto, Brazil
Thomé C:: Department of Internal Medicine, Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of São Paulo, Ribeirao Preto, Brazil
Jacomo RH:: Department of Internal Medicine, Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of São Paulo, Ribeirao Preto, Brazil
Melo RA:: Department of Internal Medicine, University of Pernambuco and Fundação HEMOPE, Recife, Brazil
Bittencourt R:: Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Pasquini R:: Hematology Division, Federal University of Paraná, Curitiba, Brazil
Pagnano K:: Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil
Glória AB:: Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil
Chauffaille Mde L:: Hematology and Transfusion Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil
Athayde M:: Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil
Chiattone CS:: Hematology Division, Santa Casa Medical School, Sao Paulo, Brazil
Mito I:: Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Bendlin R:: Hematology Division, Federal University of Paraná, Curitiba, Brazil
Souza C:: Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil
Bortolheiro C:: Hematology Division, Santa Casa Medical School, Sao Paulo, Brazil
Coelho-Silva JL:: Department of Genetics, Federal University of Pernambuco, Recife, Brazil
Grimwade D:: Department of Medical and Molecular Genetics, King's College London School of Medicine, London, United Kingdom
Ganser A:: Department of Hematology, Hannover Medical School, Hannover, Germany
Lo-Coco F:: Department of Biopathology, University Tor Vergata, Rome, Italy

Santa Lucia Foundation, Rome, Italy
Löwenberg B:: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands

and
Sanz MA:: Department of Hematology, Valencia University Medical School, Valencia, Spain
Rego EM:: Department of Internal Medicine, Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of São Paulo, Ribeirao Preto, Brazil

Campos de estudio

Proyectos asociados

RED DE INVESTIGACION COOPERATIVA DE CANCER

RD06/0020/0031 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

CREACION Y MEJORA DE INFRAESTRUCTURAS EN MEDICINA REGENERATIVA

Investigador Principal: FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA

PLE2009-0141 ACI-PLAN E . MINISTERIO DE CIENCIA E INNOVACION; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009