Retroviral insertional mutagenesis in murine promonocytic leukemias: c-myb and Mml1.
Curr Top Microbiol Immunol
; 211: 191-9, 1996.
Article
em En
| MEDLINE
| ID: mdl-8585950
ABSTRACT
Studies have focused on two genetic loci, c-myb and Mml1, whose activation by retroviral insertional mutagenesis contribute to promonocytic leukemia in our acute monocytic leukemia (AMoL) model. Multiple mechanisms of activation of c-myb by retroviral insertional mutagenesis implicate both transcriptional deregulation and protein truncation in conversion of this proto-oncogene to an oncogene. Because transformation by c-Myb can be viewed as a block to differentiation our studies moved into two in vitro systems to evaluate effects of truncated forms of c-Myb on cytokine induced maturation of myeloid progenitors to the granulocyte and macrophage lineages. Deregulated expression of truncated and full length c-Myb did not result in maintenance of the myelomonocytic progenitor state but rather a block in differentiation at intermediate to late steps in the maturation processes of myelomonocytic cells. Our results argue that inhibition of differentiation is due to c-Myb's ability to maintain the proliferative state of cells. Interestingly, the phenotype of continuously proliferating monocytic cells resembles that of the tumor cell phenotype. Recently we identified a new target of integration, Mml1, which is rearranged in ten promonocytic leukemias that do not have c-myb rearrangements. This locus which was mapped to chromosome 10 is presently being characterized.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielomonocítica Aguda
/
Mutagênese Insercional
/
Proteínas Proto-Oncogênicas c-myc
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Integração Viral
/
Vírus da Leucemia Murina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article