TY - JOUR
TI - Predominantly post-transcriptional regulation of activation molecules in
chronic lymphocytic leukemia: The case of transferrin receptors
AU - Chiotoglou, Ioanna
AU - Smilevska, Tatjana
AU - Samara, Maria
AU - Likousi,
AU - Sophia
AU - Belessi, Chrysoula
AU - Athanasiadou, Ioanna
AU - Stavroyianni,
AU - Niki
AU - Samara, Stavroula
AU - Laoutaris, Nikolaos
AU - Vamvakopoulos,
AU - Nikolaos
AU - Anagnostopoulos, Achilles
AU - Fassas, Athanasios and
AU - Stamatopoulos, Kostas
AU - Kollia, Panagoula
JO - BLOOD CELLS MOLECULES AND DISEASES
PY - 2008
VL - 41
TODO - 2
SP - 203-209
PB - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN - 1079-9796
TODO - 10.1016/j.bcmd.2008.05.003
TODO - transferrin receptor; transcription; B cell; CLL
TODO - 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.
ER -