It is widely accepted that the neoplastic B cells from patients with
chronic lymphocytic leukemia (CLL) respond poorly to common
mitogens. The fungal metabolite
cytochalasin B (0.5 micrograms/ml) is a weak
mitogen for normal lymphocytes. However, when peripheral blood lymphocytes from 19 patients with CLL of B cell origin (B-CLL) were cultured with 0.5 micrograms
cytochalasin B/ml, significant new
DNA synthesis ( [14C]
thymidine incorporation) occurred in 18. Stimulation indices with
cytochalasin B varied widely (range = 1.9-28.2, mean +/- SD = 10.6 +/- 7.5; delta cpm range = 1,157-153,818; n = 26) but in 11 cases exceeded those seen with
concanavalin A (Con A),
phytohemagglutinin, or
pokeweed mitogen. In all 11, the mitogenic response to
cytochalasin B exceeded that to
pokeweed mitogen, which is believed to be a T cell-dependent B cell
mitogen. In three cases, the responses to
cytochalasin B were 8.6, 3.5, and 2.3 times greater than those to Con A. As with other
mitogens, the
DNA synthetic response to
cytochalasin B was time and dose dependent. Peak
thymidine incorporation occurred at 72-88 h and declined thereafter. Significant mitogenic effects were observed with 0.1-5 micrograms
cytochalasin B/ml with a peak at 0.5-2 micrograms/ml. Stimulated
DNA synthesis was abolished by 1 mM
hydroxyurea. Cells from two patients with B-CLL were separated by rosetting with sheep erythrocytes (E). Depletion of E-rosette-positive cells from the CLL cell population abolished the response to Con A but did not affect the response to
cytochalasin B.
Cytochalasin B is a potent
mitogen for B-CLL cells and may be useful in cytogenetic studies of this often indolent
neoplasm.