PLZF-mediated control on VLA-4 expression in normal and leukemic myeloid cells.
The promyelocytic leukemia zinc-finger protein (PLZF) is a transcriptional repressor. To investigate the role of PLZF in the regulation of cytoadhesion molecules involved in the mobilization of hemopoietic cells, we have analysed PLZF and very late antigen 4 (VLA-4) expression in normal and leukemic cells. In hematopoiesis, we found a negative correlation between PLZF and VLA-4 expression, except for the megakaryocytic lineage. In contrast, we observed a positive correlation between PLZF and VLA-4 expression in a panel of acute myeloid leukemia (AML) samples. In K562 cells expressing PLZF (K562-PLZF), we found that the expression of VLA-4 and c-kit was downmodulated. We have investigated the possibility for VLA-4 or the c-kit receptor to be direct target genes of PLZF in K562-PLZF cells and identified a PLZF DNA-binding site within the VLA-4 promoter. Furthermore, decrease in VLA-4 expression was associated with loss of adhesion on fibronectin-coated plates, which promotes drug-induced apoptosis of K562-PLZF cells. Our findings indicate that VLA-4 is a potential target gene of PLZF. However, in primary AMLs the control of PLZF on VLA-4 expression is lost. Altogether, we suggest that VLA-4 modulation by PLZF may represent an important step in the control of normal and leukemic cell mobilization.
Quaranta
M T
MT
1Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Spinello
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Testa
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Mariani
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Diverio
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Foà
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Peschle
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Labbaye
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D000208:Acute Disease; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D039041:Integrin alpha4beta1; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger; D014157:Transcription Factors; C092037:ZBTB16 protein, human