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Abstract
The in vitro responses of the JOK-1 cell line, derived from a patient with hairy cell leukemia, to chemical inducers of differentiation have been investigated. Morphology, surface markers, and cell kinetics were studied following continuous exposure to the inducers for periods ranging from 1-7 days. Non-induced JOK-1 cells expressed sIgM, B-1 and cALLa antigens and C3 receptors. Following exposure to 2% DMSO, 10('-7) to 10('-11) ng TPA or 5 mM HMBA the cells underwent a phenotypic change from lymphoblastoid to monocytoid. In the presence of TPA they became adherent and developed dendritic-like processes. Concomitant with these morphologic changes, there was a decrease in sIgM and cALLa and variable expression of C3 receptors. No monocyte/macrophage associated antigens were detected, and the induced cells failed to enter a logarithmic growth phase. The DMSO and TPA treated cells were arrested in the G(,1) compartment of the cell cycle. The JOK-1 cells and their supernatant significantly inhibited mitogen induced lymphocyte proliferation.
Growth of JOK-1 was initiated in nude mice by irradiating them with 2 Gy per week x3, then injecting JOK-1 cells with X-irradiated HT-1080 sarcoma cells s.c. The latter are believed to produce an angiogenesis factor, which promotes neo-vascularization of the tumor. Thereafter, tumors were transplanted as 1 mm fragments into non-irradiated hosts and without HT-1080 cells. To determine if there was an in vivo growth inhibitory effect, mice were given 2% DMSO continuously in their drinking water, or i.p. injections of HMBA every 8 hours for 9 days. Treatment was initiated when the tumor mass had reached 100 mg. In 2 of 3 experiments DMSO had a potent growth inhibitory effect on JOK-1 cells but eventually tumors in control animals spontaneously regressed making comparisons difficult. Similar effects were seen with HMBA at 800 mg/kg. Histopathologic examination of regressing tumors in control and experimental animals revealed marked necrosis without any evidence of cellular differentiation. Due to tumor variability within groups, the data was statistically not significant. Studies with patients who had this disease showed that NK activity was absent but could be partially restored with IL-2.
