Predominantly post-transcriptional regulation of activation molecules in chronic lymphocytic leukemia: the case of transferrin receptors.
Blood Cells Mol Dis
; 41(2): 203-9, 2008.
Article
em En
| MEDLINE
| ID: mdl-18621559
ABSTRACT
Transcriptional and post-transcriptional control mechanisms have a differential impact on cellular physiology depending on activation status. Several lines of evidence suggest that chronic lymphocytic leukemia (CLL) malignant B cells resemble antigen-experienced and activated B cells. In the present study, we investigated the expression of transferrin receptor 1 (TfR1, CD71), one of the "classical" markers up-regulated upon B-cell activation, and TfR2, a novel receptor for transferrin, in peripheral blood CD19+ B cells from ten healthy individuals and 76 patients with CLL so as to gain insight into potential disease-related differences in underlying regulatory mechanisms. Marked differences in the production and expression of these receptors were detected in malignant but not in normal B cells. Specifically, TfR1 mRNA and protein levels were significantly higher in comparison to TfR2, both in normal and malignant B cells. Furthermore, discrepancies between TfR mRNA and protein expression were observed in CLL; in contrast, mRNA and protein expression levels were generally concordant in normal B cells. Exposure to actinomycin D decreased TfR1 and TfR2 mRNA levels in normal CD19+ B cells but had no effect on CLL malignant cells. The protein synthesis inhibitor cycloheximide had opposing effects in normal vs. CLL malignant B cells thus, TfR1 and TfR2 mRNA levels were increased in normal B cells, whereas they were unaffected or even suppressed in CLL malignant B cells. These results allude to differential regulation of TfR1 and TfR2 expression in normal B cells vs. CLL. In normal B cells, transcriptional mechanisms exert a critical control over TfR1 and TfR2 expression, whereas in CLL post-transcriptional mechanisms seem to play a complementary and perhaps more important role. This type of control appears to be especially suited for modulation of genes implicated in proliferation of activated cells, like CLL malignant B cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores da Transferrina
/
Linfócitos B
/
Leucemia Linfocítica Crônica de Células B
/
Regulação Neoplásica da Expressão Gênica
Tipo de estudo:
Observational_studies
Limite:
Humans
Idioma:
En
Revista:
Blood Cells Mol Dis
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Grécia