Predominantly post-transcriptional regulation of activation molecules in chronic lymphocytic leukemia: the case of transferrin receptors

Blood Cells Mol Dis. Sep-Oct 2008;41(2):203-9. doi: 10.1016/j.bcmd.2008.05.003. Epub 2008 Jul 14.

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.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, CD / analysis
  • Antigens, CD / genetics
  • B-Lymphocytes / chemistry*
  • Case-Control Studies
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • RNA, Messenger / analysis
  • Receptors, Transferrin / analysis*
  • Receptors, Transferrin / genetics
  • Up-Regulation

Substances

  • Antigens, CD
  • CD71 antigen
  • RNA, Messenger
  • Receptors, Transferrin
  • TFR2 protein, human
  • Dactinomycin
  • Cycloheximide