Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Hypoxia-related gene expression profile in childhood acute lymphoblastic leukemia: prognostic implications

Texto completo
Autor(es):
Mostrar menos -
Silveira, Vanessa S. [1] ; Freire, Bruno M. R. [1] ; Borges, Kleiton S. [2] ; Andrade, Augusto F. [2] ; Cruzeiro, Gustavo A. V. [1] ; Sabino, Joao Paulo J. [3] ; Glass, Mogens Lesner [3] ; Yunes, Jose Andres [4] ; Brandalise, Silvia Regina [4] ; Tone, Luiz Gonzaga [2, 1] ; Scrideli, Carlos Alberto [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Estadual Campinas, Ctr Infantil Boldrini, Campinas, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Leukemia & Lymphoma; v. 55, n. 8, p. 1751-1757, AUG 2014.
Citações Web of Science: 7
Resumo

A cellular hypoxic condition is a key event in several human cancers, but knowledge about its role in childhood acute lymphoblastic leukemia (ALL) is very limited. In the present study, the gene expression profile of hypoxia-related genes (HIF1A, CA9, VEGF and SCL2A1) was evaluated in bone marrow samples of 113 pediatric patients. HIF1A mRNA up-regulation was significantly associated with higher 5-year event-free survival rates in patients with B-ALL as well as in the overall ALL population in both univariate and multivariate analysis (p = 0.023 and p = 0.041, respectively). In gene expression analysis, low oxygen levels promoted HIF1A activation in a time-dependent manner, in both ALL cell lines. In vitro cytotoxic assays suggested an initial trend toward hypoxia-related resistance in the first 24 h, but evaluation at later time points (48-72 h) clearly showed that there was no relevant difference in drug response when comparing hypoxic and normal oxygen level conditions. Modulation of mRNA expression of several hypoxia-related genes was also observed after hypoxic exposure in a cell specific manner, suggesting that HIF1A mRNA expression could play a different role in specific subtypes of leukemia. Despite the remaining questions regarding hypoxia-mediated mechanisms, these findings could be helpful to provide new insights into the role of hypoxia in childhood ALL. (AU)

Processo FAPESP: 10/07020-9 - Estudos moleculares em neoplasias da criança e do adolescente: assinatura de microRNAs e estudos funcionais de genes candidatos a terapia alvo
Beneficiário:Carlos Alberto Scrideli
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/06067-1 - Avaliação do silenciamento dos genes SHOC2 e XPO7, associados à resistência à quimioterapia, em linhagens celulares de leucemia linfóide aguda
Beneficiário:Vanessa da Silva Silveira
Linha de fomento: Bolsas no Brasil - Pós-Doutorado