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PLZF-mediated control on VLA-4 expression in normal and leukemic myeloid cells

Abstract

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.

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Acknowledgements

We thank G Loreto for the preparation of the figures. This work was supported by institutional grants from the Italian Ministry of Health to CL and UT, Associazione Italiana per la Ricerca sul Cancro (AIRC) to RF, and Italy National Grants (Progetto Oncotecnologico, Programma Nazionale Cellule Staminali) to CP.

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Quaranta, M., Spinello, I., Testa, U. et al. PLZF-mediated control on VLA-4 expression in normal and leukemic myeloid cells. Oncogene 25, 399–408 (2006). https://doi.org/10.1038/sj.onc.1209060

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