Cytochalasin B is a potent mitogen for chronic lymphocytic leukemia cells in vitro.
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.
D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D003571:Cytochalasin B / Q000494:pharmacology*; D003572:Cytochalasins / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007621:Karyotyping; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D012397:Rosette Formation
D003572:Cytochalasins; D008934:Mitogens; C031218:cytochalasin A; D003571:Cytochalasin B; D004247:DNA; D004121:Dimethyl Sulfoxide