Predominantly post-transcriptional regulation of activation molecules in chronic lymphocytic leukemia: the case of transferrin receptors.
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.
Chiotoglou
Ioanna
I
Laboratory of Cytogenetics and Molecular Genetics, School of Medicine, University of Thessaly, 41222 Larissa, Greece.
Smilevska
Tatjana
T
Samara
Maria
M
Likousi
Sophia
S
Belessi
Chrysoula
C
Athanasiadou
Ioanna
I
Stavroyianni
Niki
N
Samara
Stavroula
S
Laoutaris
Nikolaos
N
Vamvakopoulos
Nikolaos
N
Anagnostopoulos
Achilles
A
Fassas
Athanasios
A
Stamatopoulos
Kostas
K
Kollia
Panagoula
P
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D001402:B-Lymphocytes / Q000737:chemistry*; D016022:Case-Control Studies; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
D015703:Antigens, CD; C068126:CD71 antigen; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D003609:Dactinomycin; D003513:Cycloheximide