Hypoxia-related gene expression profile in childhood acute lymphoblastic leukemia: prognostic implications.
Leuk Lymphoma
; 55(8): 1751-7, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24160851
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Leucêmica da Expressão Gênica
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
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Transcriptoma
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Hipóxia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
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Child, preschool
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Humans
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Infant
Idioma:
En
Revista:
Leuk Lymphoma
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article