NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice.
EMBO J
; 20(3): 350-61, 2001 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-11157742
ABSTRACT
Here we describe hemopoietic chimeras serving as a mouse model for NUP98-HOXA9-induced leukemia, which reproduced several of the phenotypes observed in human disease. Mice transplanted with bone marrow cells expressing NUP98-HOXA9 through retroviral transduction acquire a myeloproliferative disease (MPD) and eventually succumb to acute myeloid leukemia (AML). The NUP98 portion of the fusion protein was shown to be responsible for transforming a clinically silent pre-leukemic phase observed for Hoxa9 into a chronic, stem cell-derived MPD. The co-expression of NUP98-HOXA9 and Meis1 accelerated the transformation of MPD to AML, identifying a genetic interaction previously observed for Hoxa9 and Meis1. Our findings demonstrate the presence of overlapping yet distinct molecular mechanisms for MPD versus AML, illustrating the complexity of leukemic transformation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Leucemia Experimental
/
Proteínas de Fusão Oncogênica
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Complexo de Proteínas Formadoras de Poros Nucleares
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Canadá