Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia

Several features are characteristic for hairy cell leukemia (HCL). Among th ose are pancytopenia, bone marrow fibrosis, and the appearance of a defined tumor cell phenotype in peripheral blood (PB), bone marrow (BM), and splee n. Hairy cells (HC) coexpress antigens specific for B lymphocytes and monoc ytes/macrophages and thus the malignant cell does not seem to be restricted to a defined lineage. When serum or bone marrow aspirate was screened by e nzyme-linked immunosorbent assay (ELISA) for basic fibroblast growth factor (bFGF), specimen derived from HCL (serum: mean value, 29 pg/mL; BM aspirat e: mean value, 641 pg/mL) contained significantly higher levels than those from healthy subjects. To study whether peripheral blood mononuclear cells (PBMC) derived from patients suffering from HCL and healthy donors (HD) wer e capable of producing bFGF, culture supernatant (conditioned medium, [CMI) was tested for the presence of this cytokine. While bFGF was not detectabl e in cell cultures from HD, HCL-derived CM contained relatively high levels of bFGF. CM was successfully used for stimulation of mesenchymal cell prol iferation, which could be inhibited by a neutralizing anti-bFGF antibody. C ellular activation by pokeweed mitogen (PWM) or the combination of 12-o-tet radecanoyl-phorbol-13-acetate (TPA) plus calcium ionophore (Ca-lp) led to a n enhanced mRNA expression. Results of Western blot experiments showed that HC synthesize at least three isoforms (approximately 18, 23, and 25 kD), b ut only the 23-kD isoform is exported. To assess the nature of the producer cell, double immunofluorescence analysis using a bFGF-specific and an anti -CD11c monoclonal antibody (MoAb) was undertaken. The majority of cells sco ring positive for CD11c were also reactive with the anti-bFGF MoAb. Further more, enrichment of CD19/CD11c-positive cells correlated with enhanced bFGF levels, thereby supporting the argument for HC being the producer cells of bFGF A biological function of bFGF in HCL might be mediation of chemoresis tance, as 2-chlorodeoxyadenosine (5-CdA)-induced inhibition of cell prolife ration can be reversed by bFGF. Endogenous bFGF production by HC is not aff ected by this purine analogue and 2-CdA-induced apoptosis is diminished in bFGF-producing HC as compared with normal PBMC. Therefore, bFGF expression by HC might be important for resistance to chemotherapy and survival of the malignant cells. (C) 1999 by The American Society of Hematology.