Tumor necrosis factor modulates CD 20 expression on cells from chronic lymphocytic leukemia: A new role for TNF alpha?

Sivaraman, S.; Deshpande, Chetan; Ranganathan, Raghuveer; Huang, Xiaoke; Jajeh, Ahmad; O’Brien, Teresa; Huang, Ray Win; Gregory, Stephanie A.; Venugopal, Parameswaran; Preisler, Harvey D.

doi:10.1002/1097-0029(20000801)50:3<251::aid-jemt9>3.0.co;2-7

Cited by 20 publications

(8 citation statements)

References 27 publications

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“…Discrepancies between our results and other reports could be explained by differences in chemicals for CD20 binding capacity/expression and in technical methods. [14][15][16]26 According to Venugopal et al, CD20 expression on CLL B lymphocytes is up-regulated by a variety of cytokines, including IL-4, TNF-α and GM-CSF. 14 However, other data 27 stand in contrast with these results, thus supporting our own data.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Rituximab Efficiency in Chronic Lymphocytic Leukemia by CpG‐Mediated Upregulation of CD20 Expression Independently of PU.1

Mankaï

Buhé

Hammadi

et al. 2009

Annals of the New York Academy of Sciences

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Lipopolysaccharide (LPS), CpG-containing phosphothioate oligonucleotides (CpG) and various cytokines impact chronic lymphocytic leukemia (CLL) B cells. For example, they influence cell cycle entry, expression of co-receptors, and CD20. Rituximab (RTX), for which CD20 molecule is the target, proved to be less efficient in CLL than in lymphoma. This is accounted for by a lower CD20 level in the former than in the latter B lymphocytes. CD20 transcription is mediated by four transcription factors, of which only purine-rich box-1 (PU.1) is reduced in CLL. We thus examined the effects of LPS, CpG, tumor necrosis factor-alpha, interferon-alpha, interleukin (IL)-3, IL-4, IL-21, granulocyte macrophage-colony stimulating factor (CSF), and granulocyte-CSF on the transcription of PU.1, and the subsequent expression of CD20. It appeared that CpG was unique in that it raised the membrane expression of CD20 on malignant B cells, owing to a PU.1 independent increase in its gene transcription. Moreover, RTX-induced complement-mediated lysis was also ameliorated. Thus, CpG accelerates the transcription of CD20 independently of PU.1, and thereby improves the efficacy of RTX in CLL.

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Section: Discussionmentioning

confidence: 99%

Improvement of Rituximab Efficiency in Chronic Lymphocytic Leukemia by CpG‐Mediated Upregulation of CD20 Expression Independently of PU.1

Mankaï

Buhé

Hammadi

et al. 2009

Annals of the New York Academy of Sciences

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“…Recent studies have reported that IL-4, GM-CSF, TNF-␣, and IFN-␣ are able to induce CD20 surface expression on B cells from CLL patients (55)(56)(57)(58). However, the mechanisms regulating the expression of CD20 remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms

Wojciechowski

Marshall

et al. 2005

The Journal of Immunology

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Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted cells. Although the majority of B cell malignancies express the CD20 Ag, only ∼50% of patients will respond to single-agent rituximab. The available data suggest that a decreased CD20 expression could account for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. We evaluated the effect of the immune modulator agent bryostatin-1 on the expression of CD20 in non-Hodgkin’s lymphoma cells. Using the B cell lines, DB and RAMOS, as well as tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The enhanced expression of CD20 was associated with increased transcriptional activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected. The effect of bryostatin-1 on CD20 expression in non-Hodgkin’s lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the first time that ERK phosphorylation is required for the up-regulated expression of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and rituximab could be a valuable combined therapy for B cell malignancies.

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“…In clinical applications, the efficacy of Rituximab seems to fade after a period of months, leading to Rituximab resistance. The Recent studies have reported that bryostatin-1, interleukin-4, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon-α are all able to induce CD20 surface expression [8][9][10][11][12][13]. However, the mechanisms regulating the expression of CD20 remain poorly understood, even though these cytokines are well known to cause robust intracellular oxidative bursts [14,15].…”

Section: Introductionmentioning

confidence: 99%

Regulation of CD20 expression by radiation-induced changes in intracellular redox status

Gupta

Crosby

Almasan

et al. 2008

Free Radical Biology and Medicine

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Increasing the levels of CD20 expression in cells that harbor low CD20 levels may enhance their responsiveness to CD20-specific antibody therapies. Here, we examined the regulation of CD20 expression after treatment with 0.5-2.0 Gy X-irradiation and hydrogen peroxide (H 2 O 2 ), in the presence or absence of known antioxidants, in the Burkitt lymphoma cell lines Daudi and Raji. Irradiation of cells enhanced cell-surface CD20 expression; the kinetics and extent of this change were cell-type specific and time-dependent. The kinetics of reactive oxygen species generation and changes in mitochondrial membrane potential after irradiation were also correlated with changes in CD20 expression. Raji and Daudi cells treated with H 2 O 2 showed a 2-to 2.5-fold increase in CD20 expression at 12 and 20 h, respectively. Buthionine sulfoximine, which depletes glutathione, also increased surface CD20, whereas antioxidants, such as PEG-catalase, PEG-SOD, vitamin C, and amifostine, decreased CD20 expression induced by radiation or H 2 O 2 . The antioxidant-mediated decrease in CD20 expression induced by radiation or H 2 O 2 suggests a mechanism involving redox regulation. These results demonstrate the critical role of radiationinduced oxidative stress in CD20 expression and may have implications for defining and improving the efficacy of CD20-targeted antibody therapy and radioimmunotherapy. Keywords CD20; Ionizing radiation; Reactive oxygen species; Antioxidants; Mitochondria; Mitochondrial membrane potential; Free radicals The CD20 transmembrane protein is exclusively expressed on B cells. It appears during the pre-B-cell stage, but is absent during the earlier or later stages of B cell differentiation, such as in antibody-secreting plasma cells [1,2]. CD20 has received extensive evaluation as an ideal target for immunotherapy and radioimmunotherapy, in part because of its ubiquitous expression on target cells, stable localization within the cell membrane, and absence from normal stem cells [3]. Rituximab, a chimeric monoclonal anti-CD20 antibody, has been used extensively in the treatment of low-grade B cell lymphomas, such as non-Hodgkin lymphoma (NHL) and other related pathologies. In clinical applications, the efficacy of Rituximab seems to fade after a period of months, leading to Rituximab resistance. The Recent studies have reported that bryostatin-1, interleukin-4, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon-α are all able to induce CD20 surface expression [8][9][10][11][12][13]. However, the mechanisms regulating the expression of CD20 remain poorly understood, even though these cytokines are well known to cause robust intracellular oxidative bursts [14,15]. Recently, it was shown that the bryostatin-1-induced increase of CD20 was regulated at the transcriptional level. The effect of bryostatin-1 on CD20 expression in NHL-derived cells was apparently mediated through the MAPK/ERK signal transduction pathway and involved protein kinase C [13]. Our group has previous...

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Tumor necrosis factor modulates CD 20 expression on cells from chronic lymphocytic leukemia: A new role for TNF alpha?

Cited by 20 publications

References 27 publications

Improvement of Rituximab Efficiency in Chronic Lymphocytic Leukemia by CpG‐Mediated Upregulation of CD20 Expression Independently of PU.1

Improvement of Rituximab Efficiency in Chronic Lymphocytic Leukemia by CpG‐Mediated Upregulation of CD20 Expression Independently of PU.1

Enhanced Expression of CD20 in Human Tumor B Cells Is Controlled through ERK-Dependent Mechanisms

Regulation of CD20 expression by radiation-induced changes in intracellular redox status

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