title: 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.
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.
authors.affiliation: Clinical Hematology and Clinical Diagnostics, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno-ku, Osaka, Japan.
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Koh
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamane
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takubo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tatsumi
mesh_terms: 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
chemical_list: 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