TY - JOUR
T1 - High Δnp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia
AU - Lucena-Araujo, Antonio R.
AU - Kim, Haesook T.
AU - Thomé, Carolina
AU - Jacomo, Rafael H.
AU - Melo, Raul A.
AU - Bittencourt, Rosane
AU - Pasquini, Ricardo
AU - Pagnano, Katia
AU - Glória, Ana Beatriz F.
AU - De Lourdes Chauffaille, Maria
AU - Athayde, Melina
AU - Chiattone, Carlos S.
AU - Mito, Ingrid
AU - Bendlin, Rodrigo
AU - Souza, Carmino
AU - Bortolheiro, Cristina
AU - Coelho-Silva, Juan L.
AU - Schrier, Stanley L.
AU - Tallman, Martin S.
AU - Grimwade, David
AU - Ganser, Arnold
AU - Berliner, Nancy
AU - Ribeiro, Raul C.
AU - Lo-Coco, Francesco
AU - Löwenberg, Bob
AU - Sanz, Miguel A.
AU - Rego, Eduardo M.
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015/11/12
Y1 - 2015/11/12
N2 - 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 ΔNp73/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 ΔNp73/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 ΔNp73/TAp73 ratio is an important determinant of clinical responsein APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.
AB - 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 ΔNp73/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 ΔNp73/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 ΔNp73/TAp73 ratio is an important determinant of clinical responsein APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.
UR - http://www.scopus.com/inward/record.url?scp=84948948591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948948591&partnerID=8YFLogxK
U2 - 10.1182/blood-2015-01-623330
DO - 10.1182/blood-2015-01-623330
M3 - Article
C2 - 26429976
AN - SCOPUS:84948948591
SN - 0006-4971
VL - 126
SP - 2302
EP - 2306
JO - Blood
JF - Blood
IS - 20
ER -
