Τίτλος:
Predominantly post-transcriptional regulation of activation molecules in
chronic lymphocytic leukemia: The case of transferrin receptors
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 tell 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 genies implicated in proliferation of activated
cells, like CLL malignant B cells. (C) 2008 Published by Elsevier Inc.
Συγγραφείς:
Chiotoglou, Ioanna
Smilevska, Tatjana
Samara, Maria
Likousi,
Sophia
Belessi, Chrysoula
Athanasiadou, Ioanna
Stavroyianni,
Niki
Samara, Stavroula
Laoutaris, Nikolaos
Vamvakopoulos,
Nikolaos
Anagnostopoulos, Achilles
Fassas, Athanasios and
Stamatopoulos, Kostas
Kollia, Panagoula
Περιοδικό:
BLOOD CELLS MOLECULES AND DISEASES
Εκδότης:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Λέξεις-κλειδιά:
transferrin receptor; transcription; B cell; CLL
DOI:
10.1016/j.bcmd.2008.05.003
