Myeloproliferative disorder and leukaemia in mice induced by different classes of constitutive mutants of the human IL-3/IL-5/GM-CSF receptor common beta subunit.
Oncogene
; 18(51): 7190-9, 1999 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-10602472
ABSTRACT
Several constitutively active mutant forms of the common beta subunit of the human IL-3, IL-5 and GM-CSF receptors (hbetac), which enable it to signal in the absence of ligand, have recently been described. Two of these, V449E and I374N, are amino acid substitutions in the transmembrane and extracellular regions of hbetac, respectively. A third, FIDelta, contains a 37 amino acid duplication in the extracellular domain. We have shown previously that when expressed in primary murine haemopoietic cells, the extracellular mutants confer factor-independence on cells of the neutrophil and monocyte lineages only, whereas V449E does so on all cell types of the myeloid and erythroid compartments. To study the in vivo effects and leukaemic potential of these mutants, we have expressed all three in mice by bone marrow reconstitution using retrovirally infected donor cells. Expression of the extracellular mutants leads to an early onset, chronic myeloproliferative disorder marked by elevations in the neutrophil, monocyte, erythrocyte and platelet lineages. In contrast, expression of V449E leads to an acute leukaemia-like syndrome of anaemia, thrombocytopaenia and blast cell expansion. These data support the possibility that activating mutations in hbetac are involved in haemopoietic disorders in man.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Leucemia Experimental
/
Receptores de Interleucina-3
/
Mutação Puntual
/
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos
/
Receptores de Interleucina
/
Transtornos Mieloproliferativos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article