Cytochalasin B is a potent mitogen for chronic lymphocytic leukemia cells in vitro.

Abstract

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.

• Authors: R A Larson, S Yachnin
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 72 Issue 4 Pg. 1268-76 (Oct 1983) ISSN: 0021-9738 [Print] United States
• PMID: 6630510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytochalasins
• Mitogens
• cytochalasin A
• Cytochalasin B
• DNA
• Dimethyl Sulfoxide

Topics

• Cell Transformation, Neoplastic (immunology)
• Cytochalasin B (pharmacology)
• Cytochalasins (pharmacology)
• DNA (biosynthesis)
• Dimethyl Sulfoxide (pharmacology)
• Dose-Response Relationship, Immunologic
• Female
• Humans
• Karyotyping
• Kinetics
• Leukemia, Lymphoid (genetics, immunology)
• Lymphocyte Activation
• Male
• Mitogens (pharmacology)
• Rosette Formation