Differential effects of fibroblast growth factor-4, epidermal growth factor and transforming growth factor-beta1 on functional development of stromal layers in acute myeloid leukemia

Leuk Res. 2002 Oct;26(10):933-8. doi: 10.1016/s0145-2126(02)00033-4.

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-beta1 (TGF-beta1) 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-beta1. 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-beta1 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-beta1 preferentially affected the primitive progenitors rather than committed ones. These results indicate that FGF-4 and TGF-beta1 differentially affect the functional development of leukemic as well as of normal stromal layers.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / pathology
  • Cell Communication / drug effects
  • Cell Count
  • Cell Culture Techniques
  • Cell Division / drug effects
  • Coculture Techniques
  • Epidermal Growth Factor / pharmacology
  • Female
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / pharmacology
  • Growth Substances / pharmacology*
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Leukemia, Myeloid / pathology*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / pharmacology
  • Stromal Cells / drug effects*
  • Stromal Cells / pathology
  • Stromal Cells / physiology
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1

Substances

  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Growth Substances
  • Proto-Oncogene Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factors
  • Epidermal Growth Factor