| Autor: |
Mihalcik SA; Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA., Tschumper RC, Jelinek DF |
| Jazyk: |
angličtina |
| Zdroj: |
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2010 Dec 15; Vol. 9 (24), pp. 4884-92. Date of Electronic Publication: 2010 Dec 15. |
| DOI: |
10.4161/cc.9.24.14156 |
| Abstrakt: |
Together, circulating BAFF and dominant receptor BAFF-R homeostatically regulate the humoral immune system. Consistently aberrant BAFF-R expression in leukemic cells reveals an intimate connection of these cells' malignant physiology to the BAFF/BAFF-R axis and also provides an additional survival mechanism to the expressing cells. In this study, we used primary cells and cell lines to interrogate the mechanisms underlying aberrant BAFF-R expression in precursor B acute lymphoblastic leukemia (precursor B-ALL) and mature B chronic lymphocytic leukemia (CLL). Here we demonstrate the aberrant expression of BAFF-R in precursor B-ALL cell lines and reveal that these cells acquire BAFF-R expression through premature transcriptional activation of the BAFF-R promoter in coordination with regulatory transcription factor c-Rel. Investigations using primary CLL cells provide a crucial counterpoint through their paucity of BAFF-R relative to their benign mature B cell counterparts, which we establish as functionally significant in its depletion of the CLL cells' BAFF-binding capacity. Furthermore, BAFF-R downregulation in CLL patients is revealed here to be restricted to the malignant compartment and mediated post-transcriptionally in order to compensate for the consistently unchanged levels of transcription factor c-Rel and BAFF-R mRNA. Finally, we present evidence that CLL cells retain endogenous mechanisms of BAFF-R regulatory control despite active receptor dysregulation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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