EXPRESSION OF BASIC FIBROBLAST GROWTH-FACTOR (BFGF) AND FGF-RECEPTORSIN HUMAN LEUKEMIC-CELLS

Recent reports have suggested that basic fibroblast growth factor (bFG F) could play a permissive role in hematopoiesis, in combination with specific colony-stimulating factors. We investigated the expression of bFGF and FGF-receptors (FGF-Rs) in leukemic cell lines of various hem atopoietic lineages. Three protein isoforms of bFGF of approximately 1 8, 22 and 24 kDa were detected in the myeloid cell line K562, but not in myelomonocytic or lymphoid (T or B) cell lines. In vitro-induced di fferentiation of K562 cells did not change the pattern of expression o f the different bFGF isoforms. Accordingly, the mRNA of bFGF was found expressed in K562, but not in other leukemic lines tested, as assayed by reverse transcript amplification (RT-PCR). Using the same techniqu e, we searched for the presence of high affinity FGF-Rs on these cells : in eight out of ten cell lines tested, mRNA for at least one FGF-R a mong FGF-RI, FGF-R3 or FGF-R4 was expressed, whereas FGF-R2 was never detected. We found that two cell lines were responsive to bFGF in diff erent biological assays: (i) in K562 myeloid cells induced to differen tiate by hemin, preincubation with bFGF and heparin increased cell via bility and decreased hemin-induced DNA fragmentation, without affectin g erythroid differentiation; and (ii) in U937 monocytic cells, the pro duction of plasminogen activator was increased by bFGF or aFGF in comb ination with heparin. Binding experiments with I-125-bFGF (up to 200 p M) in the presence of heparin revealed high affinity receptors on the K562 and U937 cell lines (1177 +/- 440 and 392 +/- 184 sites/cell, K-d = 61.7 +/- 8.6 and 43.1 +/- 13.5pM, respectively). Thus our results s trongly suggest that cells of hematopoietic origin could express funct ional FGF-receptors.