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.
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.
Koh
Ki-Ryang
KR
Clinical Hematology and Clinical Diagnostics, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno-ku, Osaka, Japan.
Ohta
Kensuke
K
Nakamae
Hirohisa
H
Hino
Masayuki
M
Yamane
Takahisa
T
Takubo
Takayuki
T
Tatsumi
Noriyuki
N
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor