scholarly journals Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo

Cancer Cell ◽  
2013 ◽  
Vol 23 (1) ◽  
pp. 77-92 ◽  
Author(s):  
Gloria Lutzny ◽  
Thomas Kocher ◽  
Marc Schmidt-Supprian ◽  
Martina Rudelius ◽  
Ludger Klein-Hitpass ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
B Cells ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Stromal Cells ◽  
Lymphocytic Leukemia ◽  
Kinase C

scholarly journals Analysis of signal transduction in B chronic lymphocytic leukemia cells

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1461-1469
Author(s):  
HG Drexler ◽  
MK Brenner ◽  
E Coustan-Smith ◽  
SM Gignac ◽  
AV Hoffbrand
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
B Cells ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Receptor Expression ◽  
Kinase C

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.

scholarly journals Protein kinase C‐β‐dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia

Stem Cells ◽  
2021 ◽  
Vol 39 (6) ◽  
pp. 819-830
Author(s):  
Franziska Heydebrand ◽  
Maximilian Fuchs ◽  
Meik Kunz ◽  
Simon Voelkl ◽  
Anita N. Kremer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Glucose Metabolism ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Lymphocytic Leukemia ◽  
Marrow Stromal Cells ◽  
Kinase C

scholarly journals Analysis of signal transduction in B chronic lymphocytic leukemia cells

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1461-1469 ◽  
Author(s):  
HG Drexler ◽  
MK Brenner ◽  
E Coustan-Smith ◽  
SM Gignac ◽  
AV Hoffbrand
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
B Cells ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Receptor Expression ◽  
Kinase C

Abstract 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.

scholarly journals Rapid expression of protooncogenes c-fos and c-myc in B-chronic lymphocytic leukemia cells during differentiation induced by phorbol ester and calcium ionophore

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1656-1663 ◽  
Author(s):  
HG Drexler ◽  
JW Janssen ◽  
MK Brenner ◽  
AV Hoffbrand ◽  
CR Bartram
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Phorbol Ester ◽  
Messenger Rna ◽  
Calcium Ionophore ◽  
Lymphocytic Leukemia ◽  
Calcium Flux ◽  
Ionophore A23187 ◽  
Kinase C

Abstract The peripheral blood mononuclear cells from patients with B-chronic lymphocytic leukemia (B-CLL) were incubated for 0.5 h to 72 h in the presence of the phorbol ester TPA, the calcium ionophore A23187, or a combination of these reagents. Using Northern blot analysis, total cellular RNA was prepared from cells harvested at different time points and hybridized with DNA clones specific for the protooncogenes c-fos and c-myc. While untreated control cells lacked detectable amounts of messenger RNA (mRNA), increase in the level of c-fos mRNA was noted as early as 0.5 h after exposure to the inducers. Peaks of c-fos and c-myc transcript accumulation were seen at 1 h and 4 h after induction, respectively. The most effective inducer was double stimulation with TPA plus A23187. The kinetics of c-fos and c-myc mRNA accumulation in B- CLL appear to be similar to those reported for normal lymphocytes that have been either activated by physiologic external stimuli or by direct activators of protein kinase C and calcium flux (such as TPA and A23187). No direct link between oncogene expression and proliferation or differentiation parameters could be established. These results document that expression of c-fos and c-myc genes, which are among the earliest events following stimulation of the protein kinase signal transduction pathway, can be successfully induced in B-CLL cells. The data provide further evidence for the hypothesis that signal transmission downstream of protein kinase C is intact in B-CLL.

scholarly journals Protein kinase C expression is deregulated in chronic lymphocytic leukemia

2013 ◽  
Vol 54 (10) ◽  
pp. 2288-2290 ◽  
Author(s):  
Nuzhat N. Kabir ◽  
Lars Rönnstrand ◽  
Julhash U. Kazi
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Kinase C

Effect of Serum and Antioxidants on the Immunogenicity of Protein Kinase C-Activated Chronic Lymphocytic Leukemia Cells

2005 ◽  
Vol 28 (1) ◽  
pp. 28-39 ◽  
Author(s):  
Caitlin Hammond ◽  
Yonghong Shi ◽  
Jenny Mena ◽  
Jelena Tomic ◽  
David Cervi ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Kinase C

198 Activated NOTCH2 links protein kinase C delta (PKC-δ) to the expression of CD23 in chronic lymphocytic leukemia (CLL) cells

Cytokine ◽  
2008 ◽  
Vol 43 (3) ◽  
pp. 286-287
Author(s):  
Josef D. Schwarzmeier ◽  
Rainer Hubmann ◽  
Martin Hilgarth ◽  
Susanne Schnabl ◽  
Dita Demirtas ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Protein Kinase C Delta ◽  
Kinase C
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