Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1(+) leukemia.
Cancer Cell
; 19(6): 740-53, 2011 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-21665148
ABSTRACT
Imatinib has revolutionized the treatment of Bcr-Abl1(+) chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PlGF levels are elevated in CML and that PlGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PlGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of Bcr-Abl1 signaling. Anti-PlGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PlGF inhibition for (imatinib-resistant) CML.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Proteínas Gestacionales
/
Pirimidinas
/
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Proteínas de Fusión bcr-abl
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA