Phorbol ester (TPA)-induced surface membrane alterations in B-type hairy cell and lymphocytic leukemia cells

This report documents phorbol ester (TPA)-induced changes in cell morphology, and in vitro growth patterns in 9 patients with hairy cell leukemia (HCL), 21 with B-type CLL and non-Hodgkin's lymphoma in leukemic phase (NHL), and 10 with acute non lymphoblastic leukemia (ANLL). TPA caused cells from HCL to adhere strongly and produce elongated cytoplasmic extensions. Many of these cells had an appearance resembling fibroblasts, while others showed marked surface ruffling and spreading containing increased dense bodies, and phagolysosomal vacuoles as seen by transmission electron microscopy. This HCL in vitro growth pattern after TPA exposure differed from that seen in B-CLL and NHL cells, which only adhered moderately after 72 hours and readily detached in clumps. CLL and NHL-cells did not show ultrastructural features of macrophages but had either plasmacytic or HCL features. It is suggested that these different growth patterns may aid in distinguishing HCL from other B-cell neoplasias. The expression of surface markers, tartrate resistant acid phosphatase (TRAP) and Ig secretion were studied in some B-CLL, NHL and HCL cells after exposure to different concentrations of TPA for up to 6 days. Results showed that the documented changes were frequently both dose and time dependent and the most striking HCL-features were encountered after 6 days incubation with higher concentrations of TPA. However, individual variation from case to case was noted. Nevertheless, it seems that TPA induces neoplastic B-cells to mature into secreting plasmacytoid lymphocytes, and cells with features of HCL with variable expression of surface markers and TRAP.