A NEW FIBROBLAST GROWTH-STIMULATING ACTIVITY FROM THE HUMAN MEGAKARYOBLASTIC LEUKEMIA-CELL LINE ELF-153 - IN-VITRO AND IN-VIVO FINDINGS

Although the exact mech an ism for the progression of myelofibrosis in acute megakaryoblastic leukaemia is unclear, certain humoral factors released from the proliferating megakaryoblasts that are unable to sto re these factors in their defective alpha-granules, including platelet derived growth factor (PDGF), fibroblast growth factors (FGF), platel et factor-4 (PF-4), transforming growth factor-beta (TGF-beta) and bet a-thromboglobulin, could result in increased collagen synthesis by bon e marrow fibroblasts. Recently, the human megakaryoblastic leukaemia c ell 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 ha ve examined the presence of a fibroblast growth stimulating activity a nd the humoral factors that might be responsible for it in the superna tant of the human megakaryoblastic leukaemia cell line ELF-153 recentl y established in our laboratory from a patient with acute myelofibrosi s. 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 kno wn fibroblast growth stimulating humoral factors including PDGF, epith elial growth factor, TGF-alpha or beta, tumour necrosis factor-alpha, interleukin-1, 2, 4 or 6, FGF, fibronectin, PF-4 and factor VIII AG. A lso, in vivo, subcutaneous injection of ELF-153 megakaryoblastic leuka emia cells into nude mice formed, in three out of the five mice after 6 weeks, subcutaneous tumours with a very rigid texture whose histolog ical examination revealed dense infiltration by blast cells and pronou nced reticular fibrosis. Immunohistochemistry demonstrated exclusive d eposition of collagen III in the extracellular matrix whereas laminin and collagen IV were absent. Although the novel humoral factor(s) resp onsible for the present fibroblast growth stimulating activity could n ot be defined, we established an in vivo model for investigating the m echanisms involved in myelofibrosis often seen in patients with megaka ryoblastic leukaemia.