Vascular endothelial growth factor C--a potent risk factor in childhood acute lymphoblastic leukaemia: an immunocytochemical approach.

Aims: To investigate the immunocytochemical expression of vascular endothelial growth factor C (VEGF-C) and its receptors (VEGFR-2 and VEGFR-3) in childhood acute lymphoblastic leukaemia (ALL) blasts and to determine the possible role of this complex in the pathogenesis and prognosis of ALL.

Methods And Results: Bone marrow samples were taken from 120 children diagnosed with ALL. An indirect immunocytochemical procedure was performed with the use of monoclonal mouse anti-human antibodies against VEGF-C, VEGFR-2 and VEGFR-3 (diluted 1 : 100). The immunocytochemical expression of VEGF-C was confirmed exclusively in the cytoplasm of ALL lymphoblasts (the mean percentage was 36.4 +/- 7.2). It was absent from the cytoplasm of normal haematopoietic cells in the control group. No VEGFR-2 or VEGFR-3 expression was detected in the children of either the study or control groups. The risk of induction failure or leukaemic relapse was found to be significant in all VEGF-C+ patients (P < 0.0001 and P < 0.02, respectively; Fisher's exact test).

Conclusions: The absence of VEGF-C in blast cells predicts long-lasting remission in all leukaemic children. Our findings also suggest that leukaemic cell invasion, following VEGF-C-driven lymphangiogenesis, could be related to a mediating role of this peptide produced by blast cells themselves.