The role of interleukin-3 in classical Hodgkin's disease

Classical Hodgkin's disease (HD) is a peculiar form of lymphoma characterized by a low frequency of tumor cells, the so-called Hodgkin (H) and Reed/Sternberg (RS) cells, embedded in a background of non-neoplastic (reactive) cells believed to be recruited and activated by H-RS cell-derived cytokines/chemokines. How these tumor cells can survive in such a seemingly hostile environment has confused researchers. We have previously identified interleukin (IL)-3 receptor (R) expression as a common feature of classical HD and unveiled the potential role of IL-3 as a growth and anti-apoptotic factor for H-RS cells. More then 90% of malignant cells of classical HD usually express the alpha chain of the IL-3R (IL-3R(alpha)), as evidenced by immunostaining of frozen sections and cell suspensions from neoplastic lymph nodes. Consistently, HD-derived cell lines (L428, KMH2, HDLM2 and L1236) express the alpha and beta chains that form IL-3R, both at the mRNA and protein level, with a molecular size of IL-3R(alpha) identical (70 kDa) to that expressed by human myeloid cells. Exogenous IL-3 promotes the growth of cultured H-RS cells, such an effect being potentiated by IL-9 and stem cell factor (SCF) co-stimulation, and is able to partially rescue tumor cells from apoptosis induced by serum deprivation. Finally, cultured H-RS cells are able to increase the production of IL-3 by pre-activated T cells, suggesting an involvement of IL-3/IL-3R interactions in the cellular growth of HD through paracrine mechanisms. This review will outline the biological activity of IL-3 and summarize the evidence indicating IL-3 as a growth and anti-apoptotic factor for H-RS cells in classical HD.