Activation of quiescent ABL-transduced hemopoietic stem cells.
Oncogene
; 13(11): 2397-405, 1996 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-8957081
ABSTRACT
Chronic myelogenous leukemia (CML) is a hemopoietic stem cell disorder in which an activated ABL oncogene is expressed and has been shown to play an important role in disease pathogenesis. A mouse model has been established in which hemopoietic stem cells (HSCs) transduced with a retrovirus vector carrying an activated ABL oncogene can be analysed. Using this model, we now report that abl-transduced HSCs can be quiescent without causing a disease for an extended period of time. Recipient mice were able to survive more than one treatment of 5-fluorouracil (5-FU) at a dose that normally eliminates cycling hemopoietic progenitor cells; subsequently, transduced HSCs could become activated and undergo clonal expansion, resulting in abl-induced leukemic development. The disease developed in these mice was transplantable. Upon engraftment into secondary mice, previously unidentified abl-transduced HSC clones appeared. These data suggest the presence of an abl-suppressive mechanism in HSCs and have important implications to the pathogenesis of stem cell diseases and leukemic clonal evolution.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Genes abl
/
Fluoruracila
/
Transtornos Mieloproliferativos
/
Antimetabólitos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos