1. ¹Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
2. ²Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'La Sapienza' University, Rome, Italy

Correspondence: Dr C Labbaye, Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. E-mail: clabbaye@iss.it

³These two authors contributed equally to this work.

Received 12 April 2005; Revised 27 July 2005; Accepted 29 July 2005; Published online 12 September 2005.

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.