Overexpression of basic fibroblast growth factor and autocrine stimulation in acute myeloid leukemia.
Basic fibroblast growth factor (bFGF) is known to play a critical role in tumorigenesis of solid tumors. The importance of bFGF in hematological malignancies such as acute myeloid leukemia (AML) remains to be elucidated. Therefore, we determined bFGF protein expression by immunohistochemical analyses in bone marrow biopsies of patients with newly diagnosed, untreated AML. The expression of bFGF was significantly increased in AML patients [n = 81; median, 3.0 (interquartile range, 1.8-3.9) arbitrary units (AU)] as compared with controls [n = 18; 1.9 (1.5-2.3) AU]. The degree of bFGF expression did not correlate with microvessel density. bFGF/FGF receptor mRNA and bFGF protein were detected in different AML cell lines. To study autocrine growth stimulation of AML blasts, the AML cell lines HL-60, M-07e, and KG-1 were incubated with bFGF. A significant dose-dependent increase in proliferation and colony formation was observed. These effects were abrogated by the addition of a polyclonal anti-bFGF antibody. In conclusion, increased expression of bFGF in the bone marrow of AML patients seems to play an important role in the pathophysiology of AML by promoting autocrine growth stimulation of leukemic blasts.
Bieker
Ralf
R
Department of Medicine/Hematology and Oncology, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany.
Padró
Teresa
T
Kramer
Julia
J
Steins
Martin
M
Kessler
Torsten
T
Retzlaff
Stephan
S
Herrera
Federico
F
Kienast
Joachim
J
Berdel
Wolfgang E
WE
Mesters
Rolf M
RM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2