scholarly journals The Role of Tumor Necrosis Factor and ITS Soluble Receptors in Myelosuppression Developing in B-Cell Chronic Lymphocytic Leukemia

2015 ◽  
Vol 2-3 (10-11) ◽  
pp. 36-41
Author(s):  
V. Barilka ◽  
◽  
V. Matlan ◽  
S. Prymak ◽  
O. Vygovska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Lymphocytic Leukemia ◽  
Soluble Receptors ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 393-400 ◽  
Author(s):  
R Foa ◽  
M Massaia ◽  
S Cardona ◽  
AG Tos ◽  
A Bianchi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.

Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-κB/Rel–regulated inhibitors of apoptosis

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3749-3756 ◽  
Author(s):  
Gerd Munzert ◽  
Dieter Kirchner ◽  
Heike Stobbe ◽  
Lothar Bergmann ◽  
Roland M. Schmid ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Lymphocytic Leukemia ◽  
Inhibitors Of Apoptosis ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a resistance toward apoptosis-inducing agents. Nuclear factor-κB (NF-κB)/Rel has been shown to regulate the expression of antiapoptotic genes, such as members of the inhibitor of apoptosis protein (IAP) and tumor necrosis factor receptor-associated factor (TRAF) gene families. Expression and regulation of NF-κB/Rel–dependent inhibitors of apoptosis have not been collectively studied in B-CLL. We examined expression of known NF-κB/Rel–regulated antiapoptotic genes by RNAse protection assay, real-time polymerase chain reaction, and immunoblotting in patients with B-CLL. TRAF1 and to a lesser extent TRAF2 were overexpressed in B-CLL lymphocytes as compared with normal CD19+ B cells. TRAF1 overexpression did not correlate with markers of disease progression or overall survival. Furthermore, we found high constitutive expression of the IAP genes c-IAP-1, c-IAP-2, and XIAP both in normal and B-CLL lymphocytes. Focusing on the regulation of TRAF1, NF-κB/Rel activity in B-CLL nuclear extracts was shown to bind to TRAF1 promoter elements. However, IκB kinase (IKK) activity was not increased in CLL lymphocytes as compared with normal CD19+ B cells. The known IKK inhibitor sulfasalazine did not compromise TRAF1 expression. Thus, although our study revealed a common expression pattern of NF-κB/Rel–regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL.

scholarly journals Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 393-400 ◽  
Author(s):  
R Foa ◽  
M Massaia ◽  
S Cardona ◽  
AG Tos ◽  
A Bianchi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Cell Chronic Lymphocytic Leukemia

Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.

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