Beta common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice.
Blood
; 109(4): 1687-91, 2007 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-17090653
ABSTRACT
Neurofibromatosis type 1 (NF1) syndrome is caused by germline mutations in the NF1 tumor suppressor, which encodes neurofibromin, a GTPase activating protein for Ras. Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML) and lethally irradiated mice given transplants with homozygous Nf1 mutant (Nf1-/-) hematopoietic stem cells develop a fatal myeloproliferative disorder (MPD) that models JMML. We investigated the requirement for signaling through the GM-CSF receptor to initiate and sustain this MPD by generating Nf1 mutant hematopoietic cells lacking the common beta chain (Beta c) of the GM-CSF receptor. Mice reconstituted with Nf1-/-, beta c-/- stem cells did not develop evidence of MPD despite the presence of increased number of immature hematopoietic progenitors in the bone marrow. Interestingly, when the Mx1-Cre transgene was used to inactivate a conditional Nf1 mutant allele in hematopoietic cells, concomitant loss of beta c-/- reduced the severity of the MPD, but did not abrogate it. Whereas inhibiting GM-CSF signaling may be of therapeutic benefit in JMML, our data also demonstrate aberrant proliferation of Nf1-/-myeloid progenitors that is independent of signaling through the GM-CSF receptor.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mielomonocítica Crónica
/
Neurofibromatosis 1
/
Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Trastornos Mieloproliferativos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos