Analysis of signal transduction in B chronic lymphocytic leukemia cells.
Analysis of signal transduction in B chronic lymphocytic leukemia cells.
复制标题
B慢性淋巴细胞白血病细胞信号转导分析。
DOI:
10.1182/blood.v71.5.1461.1461
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发表时间:
1988
期刊:
影响因子:
20.3
通讯作者:
A. Hoffbrand
中科院分区:
文献类型:
--
作者:
H. Drexler;M. Brenner;E. Coustan;SM Gignac;A. Hoffbrand
We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL-2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B-CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells.
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DOI:
--
发表时间:
1984
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
Gordon,J;Mellstedt,H;Aman,P;Biberfeld,P;Klein,G
通讯作者:
Klein,G
影响因子:
20.3
作者:
Freedman,AS;Boyd,AW;Bieber,FR;Daley,J;Rosen,K;Horowitz,JC;Levy,DN;Nadler,LM
通讯作者:
Nadler,LM
影响因子:
20.3
作者:
Gordon,J;Mellstedt,H;Aman,P;Biberfeld,P;Björkholm,M;Klein,G
通讯作者:
Klein,G
DOI:
--
发表时间:
1985
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
Mayer,L;Crow,MK;Thompson,C
通讯作者:
Thompson,C