Although the exact mechanism for the progression of
myelofibrosis in acute megakaryoblastic leukaemia is unclear, certain humoral factors released from the proliferating megakaryoblasts that are unable to store these factors in their defective alpha-granules, including
platelet derived growth factor (PDGF),
fibroblast growth factors (FGF), platelet factor-4 (PF-4),
transforming growth factor-beta (
TGF-beta) and
beta-thromboglobulin, could result in increased
collagen synthesis by bone marrow fibroblasts. Recently, the human megakaryoblastic leukaemia cell line MEG-01 has been shown to produce both
TGF-beta and PF-4 which have enhanced the growth of bone marrow fibroblasts. Therefore, we have examined the presence of a fibroblast growth stimulating activity and the humoral factors that might be responsible for it in the supernatant of the human megakaryoblastic leukaemia cell line ELF-153 recently established in our laboratory from a patient with acute
myelofibrosis. A new fibroblast growth stimulating activity has been identified in the supernatant of the ELF-153 human megakaryoblastic leukaemia cell line that is independent of the percentage of
fetal calf serum in NRK-49F fibroblast
agar clonogenic assays and is not due to any of the known fibroblast growth stimulating humoral factors including PDGF, epithelial
growth factor,
TGF-alpha or beta, tumour
necrosis factor-alpha,
interleukin-1, 2, 4 or 6, FGF,
fibronectin, PF-4 and
factor VIII AG. Also, in vivo,
subcutaneous injection of ELF-153 megakaryoblastic leukaemia cells into nude mice formed, in three out of the five mice after 6 weeks, subcutaneous tumours with a very rigid texture whose histological examination revealed dense infiltration by blast cells and pronounced reticular
fibrosis. Immunohistochemistry demonstrated exclusive deposition of
collagen III in the extracellular matrix whereas
laminin and
collagen IV were absent.(ABSTRACT TRUNCATED AT 250 WORDS)