Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.
Blood
; 108(13): 4283-7, 2006 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-16946306
ABSTRACT
Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc-/- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/- mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma and that in vivo infusion of IFN-gamma at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-gamma conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Antivirais
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Terapia Genética
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Interferon gama
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Células Progenitoras Mieloides
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Proteína do Grupo de Complementação A da Anemia de Fanconi
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Proteína do Grupo de Complementação G da Anemia de Fanconi
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Anemia de Fanconi
Limite:
Animals
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Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos