Increased expression of delta-like ligand 4 in mycosis fungoides

In many malignancies, dysregulation of the Notch pathways, composed of 4 Notch receptors (Notch1–4) and 5 Notch ligands (Jagged1–2, Delta-like ligand-1, 3–4), is associated with their development. In mycosis fungoides, interaction between Notch1 and Jagged1 is known to activate the Notch pathways and promote the proliferation of tumour cells. However, the involve-ment of other Notch ligands has not been reported. This study investigated the roles of Delta-like ligand 4 in mycosis fungoides. Delta-like ligand 4 mRNA levels in lesional skin of patients with mycosis fungoi-des were significantly elevated compared with those of normal controls, and correlated with disease-spe-cific mortality. Immunohistochemical staining demon-strated prominent expression of Delta-like ligand 4 on vascular endothelial cells and tumour cells in mycosis fungoides lesional skin. In addition, Delta-like ligand 4 augmented the proliferation of cutaneous T-cell lymphoma cell lines. These results suggest that enhanced Delta-like ligand 4 expression may contribute directly to the progression of mycosis fungoides through proli-ferating tumour cells.