Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate.
Leukemia
; 18(10): 1656-61, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15343347
ABSTRACT
Human blood dendritic cells (DC) comprise plasmacytoid DC (PDC) and myeloid DC (MDC), which both prime antitumor T-cell responses. We prospectively monitored blood DC in 30 chronic myeloid leukemia (CML) patients before and after imatinib mesylate therapy. We found a dramatic reduction in PDC and MDC prior treatment. This reduction was associated with high plasmatic vascular endothelial growth factor (VEGF), a central regulator of angiogenesis which also participates to tumor-associated immune deficiencies. Phenotypic analysis of DC revealed in some patients a deficient expression of BDCA-4/neuropilin-1 on PDC, a molecule involved in angiogenesis and DC-T-cell interactions. High VEGF correlated to an altered Th1/Th2 balance in vivo and shifted PDC-induced T-cell polarization towards Th2 in vitro. Upon imatinib treatment, plasmatic VEGF rapidly decreased and a normal BDCA-4 expression was restored. PDC and MDC increased but did not reach the levels observed in healthy individuals. We conclude that VEGF may be a key player in blood DC deficiency in CML and we show that imatinib inhibits VEGF overproduction. Incomplete recovery of blood DC under imatinib despite VEGF normalization suggests a negative impact of this drug on dendritopoiesis in vivo and may result in a sustained defect in DC-mediated anti-CML responses.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Pirimidinas
/
Células Dendríticas
/
Leucemia Mielogênica Crônica BCR-ABL Positiva
/
Células Mieloides
/
Fator A de Crescimento do Endotélio Vascular
/
Antineoplásicos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França