FGF-2 abnormalities in B cell chronic lymphocytic and chronic myeloid leukemias.
An elevated level of fibroblast growth factor-2 (FGF-2) in peripheral blood is considered to play a role in regulating the growth of leukemia cells. Here, we show that the level of plasma FGF-2 is increased in 54% of B cell chronic lymphocytic leukemias (B-CLL) and in 44% of chronic myeloid leukemias (CML). Notably, white blood cells (WBCs) from B-CLL patients contain 18, 22 and 24 kDa isoforms of FGF-2 whereas WBCs from CML patients contain only the 24 kDa isoform. Furthermore, as cultured B-CLL WBCs release 18 kDa FGF-2 into the medium, they constitute a potential source of FGF-2 in the blood. In a receptor binding assay, 125I-FGF-2 binds weakly to B-CLL WBCs, whereas the ligand binds more strongly to CML WBCs. Correspondingly, FGF-2 is unable to activate mitogen-activated protein kinase kinase (MEK) and its substrate, extracellular signal-regulated kinase (ERK), in B-CLL cells, whereas phosphorylation of both these cell growth-related kinases increases following treatment of CML WBCs. We conclude that B-CLL WBCs secrete FGF-2 with no apparent autocrine actions. In contrast, WBCs in CML bind FGF-2 provided by other FGF-2-hyperproducing cells and activate the MEK/ERK kinase cascade, possibly to modulate cell growth.
Laboratory of Molecular Embryology, Mendel University Brno, Czech Republic.
P
P
Krejcí
D
D
Dvoráková
E
E
Krahulcová
J
J
Pacherník
J
J
Mayer
A
A
Hampl
P
P
Dvorák
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D017077:Culture Media, Conditioned; D017931:DNA Primers; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood* / Q000737:chemistry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics
D017077:Culture Media, Conditioned; D017931:DNA Primers; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2