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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 11
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Leukemia & Lymphoma; v. 55, n. 8, p. 1751-1757, AUG 2014.
Web of Science Citations: 7
Abstract

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)

FAPESP's process: 10/07020-9 - Molecular studies in neoplasias of children and adolescents: microRNAs signature and functional studies of candidate genes to target therapy
Grantee:Carlos Alberto Scrideli
Support type: Regular Research Grants
FAPESP's process: 10/06067-1 - Effect of the silencing of SHOC2 and XPO7 genes, related to chemotherapy resistance, in acute limphoblastic leukemia cell lines
Grantee:Vanessa da Silva Silveira
Support type: Scholarships in Brazil - Post-Doctorate