RGD Reference Report - Intracellular tumor necrosis factor production by T- and B-cells in B-cell chronic lymphocytic leukemia. - Rat Genome Database

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Intracellular tumor necrosis factor production by T- and B-cells in B-cell chronic lymphocytic leukemia.

Authors: Bojarska-Junak, A  Rolinski, J  Wasik-Szczepaneko, E  Kaluzny, Z  Dmoszynska, A 
Citation: Bojarska-Junak A, etal., Haematologica. 2002 May;87(5):490-9.
RGD ID: 10449463
Pubmed: PMID:12010662   (View Abstract at PubMed)

BACKGROUND AND OBJECTIVES: The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked with the production and activity of certain growth factors. Tumor necrosis factor (TNF-alpha) is important for the growth and survival of B-CLL cells. TNF-alpha promotes the proliferation of the malignant cell clone and is believed to play a role in the progression of B-CLL. The aim of our study was to examine the level of production and intracellular expression of TNF-alpha by T- and B-cells in B-CLL in correlation with stage of disease and clinical parameters. DESIGN AND METHODS: Using a three-color flow cytometry technique we analyzed intracellular TNF-alpha expression by B-cells (CD19+) and by T-cell subsets (CD3+/CD4+ and CD3+/CD8+) in peripheral blood (PB) and bone marrow (BM) from 40 patients with B-CLL and 24 healthy controls. RESULTS: A higher number of TNF-a-positive B-cells were found in PB and BM in B-CLL patients than in normal controls. In BM this difference was statistically significant (p<0.007). Likewise, in PB and BM the percentage of T-cells expressing TNF-alpha was significantly higher in B-CLL patients than in normal controls (PB: p<0.00001; BM: p<0.007). CD3+/CD4+ cells from patients displayed a lower level of intracellular TNF-alpha expression than did CD3+/CD8+ cells (PB: p<0.0001; BM: p<0.04). The number of T-cells expressing TNF-alpha in B-CLL patients was higher in those with stages III-IV than in patients with early stage disease (PB: p<0.007; BM: p<0.01). Additionally, PB and BM T-cell subsets from patients in stages III-IV had a statistically significant higher level of cytoplasmic TNF-a expression than the corresponding cells from healthy controls (PB: p<0.02; BM: p<0.05). In PB the percentage of CD4+ and CD8+ T-cells expressing cytoplasmic TNF-alpha positively correlated with the stage of disease, total tumor mass (TTM) score and lymphocytosis. In BM only the percentage of CD8 T-cells positively correlated with TTM score and lymphocytosis. The expression of TNF-alpha in leukemic B-cells did not correlate with any progression parameters of disease. INTERPRETATION AND CONCLUSIONS: The results obtained suggest that malignant B-cells are exposed to large numbers of T-cells able to synthesize and secrete TNF-alpha. Moreover, T-cells even though fewer than B-cells may be an important source of TNF-a in advanced stages of disease. This indicates that the TNF-alpha can be associated with progression of B-CLL and may be implicated in some side-effects associated with this disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
B-Cell Chronic Lymphocytic Leukemia disease_progressionIEP 10449463protein:increased expression:bone marrow more ...RGD 
B-Cell Chronic Lymphocytic Leukemia disease_progressionISOTNF (Homo sapiens)10449463; 10449463protein:increased expression:bone marrow more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information