Differential effects of fibroblast growth factor-4, epidermal growth factor and transforming growth factor-β1 on functional development of stromal layers in acute myeloid leukemia

Abstract 

The hematopoietic supporting abilities are known to be impaired in marrow stromal layers developed from patients with acute myeloid leukemia (AML). In this study, fibroblast growth factor-4 (FGF-4), epidermal growth factor (EGF) or transforming growth factor-β1 (TGF-β1) were studied to see whether these growth factors can modify the functional development of leukemic stromal layers. Adherent stromal layers from 13 patients with AML and from six non-leukemic controls were established with 3ng/ml of FGF-4, EGF or TGF-β1. Established stromal layers were washed three times and irradiated, followed by recharge of allogenic peripheral CD34 positive cells as an indicator of supportive function. Progenitor-outputs into supernatant were evaluated at biweekly interval with colony-forming assay until 6 weeks. The results showed that both leukemic and non-leukemic stromal cells established with FGF-4, but not with EGF, showed significantly higher progenitor cell-outputs compared with control stromal cells. By contrast, stromal cells developed with TGF-β1 showed significantly lower progenitor cell-outputs compared with control. These differences were significant at later than 4 weeks after the recharge of indicator cells, suggesting that the stromal layer developed with EGF or TGF-β1 preferentially affected the primitive progenitors rather than committed ones. These results indicate that FGF-4 and TGF-β1 differentially affect the functional development of leukemic as well as of normal stromal layers.

Keywords:  AML, Stroma, Marrow, FGF, EGF, TGF-β