High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis.
Leukemia
; 19(4): 580-5, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15703779
ABSTRACT
The pathophysiology of the myelodysplastic syndromes (MDS) is incompletely understood. Tumor necrosis factor (TNF)alpha levels are elevated, particularly in early-stage MDS, and apoptosis in marrow cells is upregulated. Observations in other models have shown a role for insulin-like growth factor binding protein 3 (IGFBP-3) in TNFalpha-mediated apoptosis. We observed increased levels of IGFBP-3 in the marrow plasma of patients with MDS (P = 0.005) and hypothesized that altered IGFBP-3 levels contribute to the dysregulation of hemopoiesis in MDS by affecting proliferation and apoptosis. Western analysis of marrow plasma from MDS patients revealed an increase in the ratio of intact vs fragmented IGFBP-3 in early-stage MDS (relative to controls) that decreased with MDS disease progression, suggesting increased proteolysis with more advanced disease. Thus, these results provide evidence for dysregulation of IGFBP-3 in patients with MDS. While the data are complex, they are consistent with a modulatory effect of IGFBP-3 on hemopoiesis in MDS. Conceivably, understanding these mechanisms may allow for the development of novel therapeutic strategies.
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Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
/
Síndromes Mielodisplásicas
/
Apoptose
/
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina
/
Hematopoese
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos