INTERLEUKIN-3 IS AN AUTOCRINE GROWTH-FACTOR OF HUMAN MEGAKARYOBLASTS, THE DAMI AND MEG-01 CELLS

Interleukin-3 (IL-3), a cytokine known to be produced by activated T lymphocytes, mast cells, eosinophils and neutrophils, is a potent stimulator of normal haemopoiesis, particularly megakaryocytopoiesis. However, it remains unknown whether leukaemic megakaryoblasts can produce IL-3 and whether IL-3 is involved in the pathological process of megakaryoblastic leukaemia. In this study, several human leukaemia cell lines with or without megakaryocytic features, the DAMI, MEG-01, HEL, K562, HL-60 and U937, were chosen as the models. It was first demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay that IL-3 was expressed in DAMI and MEG-01 cells, but not in other cell lines, although two erythroleukaemic cells, the HEL and K562, also possess some megakaryocytic features. Interestingly, the mRNA for IL-3 receptor was detected in nearly all the cell lines except K562 cells, suggesting that expression of IL-3 and its receptor may be dissociated in most of the cell lines and that co-expression of IL-3 and its receptor exists in megakaryoblastic cell lines, the DAMI and MEG-01. Of the cell lines which did not express IL-3 under unstimulated condition, only HEL cells were able to express IL-3 mRNA after treatment with PMA for 72 h. Furthermore, the proliferation of DAMI and MEG-01 cells could be enhanced in the presence of IL-3 and suppressed by the anti-IL-3 antibody and the IL-3 antisense oligodexyonucleotides (ODNs). These findings indicate that IL-3, as an autocrine growth factor, is involved in the growth of some megakaryocytic leukaemia cell lines.