Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras, and Cbl.
Blood
; 112(5): 2017-9, 2008 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-18566322
ABSTRACT
The NUP98-HOXD13 (NHD13) fusion gene occurs in patients with myelodysplastic syndrome (MDS) and acute nonlymphocytic leukemia (ANLL). We reported that transgenic mice expressing NHD13 develop MDS, and that more than half of these mice eventually progress to acute leukemia. The latency period suggests a requirement for at least 1 complementary event before leukemic transformation. We conducted a candidate gene search for complementary events focused on genes that are frequently mutated in human myeloid leukemia. We investigated 22 ANLL samples and found a high frequency of Nras and Kras mutations, an absence of Npm1, p53, Runx1, Kit and Flt3 mutations, and a single Cbl mutation. Our findings support a working hypothesis that predicts that ANLL cases have one mutation which inhibits differentiation, and a complementary mutation which enhances proliferation or inhibit apoptosis. In addition, we provide the first evidence for spontaneous collaborating mutations in a genetically engineered mouse model of ANLL.
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Experimental
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Proteínas de Fusão Oncogênica
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Genes ras
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Proteínas Proto-Oncogênicas c-cbl
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Mutação
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article