TLR2 may influence the behavior of the malignant clone in B-CLL

Antosz, H; Sajewicz, Joanna; Marzec-Kotarska, Barbara; Dmoszyńska, Anna; Baszak, Jacek; Jargiełło-Baszak, Małgorzata

doi:10.1016/j.bcmd.2012.03.006

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Additionally, these discrepancies may be interpreted as an evidence of increased TLR expression on CLL cells by post-transcriptional mechanisms (Arvaniti et al 2011). The studies of Antosz et al (2012) demonstrated that CLL cells stimulation using LPS and SAC ( Staphylococcus aureus Cowan I) resulted in an increase in TLR2 expression. Cellular stress proteins and products of cell degradation resulting from apoptosis are classified as endogenous TLR2 ligands.…”

Section: Discussionmentioning

confidence: 99%

TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia

Szymańska

Bojarska‐Junak

Drobiecki

et al. 2018

Arch. Immunol. Ther. Exp.

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Antigenic stimulation is considered as a possible trigger of neoplastic transformation in chronic lymphocytic leukemia (CLL). B-cell receptor plays a key role in the interactions between the microenvironment and leukemic cells; however, an important role has also been attributed to Toll-like receptors (TLRs). It is believed that disorders of TLR expression may play a part in the pathogenesis of CLL. In this study, we investigated the potential role of TLR2 in CLL by analyzing its expression on leukemic B cells in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. We assessed the frequencies of TLR2/CD19 cells by the flow cytometry method in peripheral blood of 119 patients with CLL. The percentage of TLR2/CD19 cells was significantly lower in patients with CLL as compared to the healthy volunteers. There was also a lower percentage of TLR2/CD19 cells in CLL patients with poor prognostic factors, such as ZAP70 and/or CD38 expression, 17p and/or 11q deletion. On the other hand, among patients with del(13q14) associated with favorable prognosis, the percentage of TLR2/CD19 cells was higher than among those with del(11q22) and/or del(17p13) as well as in the control group. We found an association between low percentage of CD19/CD5/TLR2 cells and shorter time to treatment. We also demonstrated the relationship between low percentage of CD19/CD5 TLR2-positive and overall survival (OS) of CLL patients. CLL patients with a proportion of 1.6% TLR2-positive B CD5 cells (according to the receiver operating characteristic curve analysis) or more had a longer time to treatment and longer OS than the group with a lower percentage of TLR2 positive cells. To sum up, the results of the study suggest that low TLR2 expression is associated with poor prognosis in CLL patients. The monitoring of CD19/CD5/TLR2 cells number may provide useful information on disease activity. Level of TLR2 expression on leukemic B cells may be an important factor of immunological dysfunction for patients with CLL. Our study suggests that TLR2 could becomes potential biological markers for the clinical outcome in patients with CLL.

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Section: Discussionmentioning

confidence: 99%

TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia

Szymańska

Bojarska‐Junak

Drobiecki

et al. 2018

Arch. Immunol. Ther. Exp.

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“…Based on our previous results and the present one, we can speculate that the expression of certain adapter proteins and IRAK4 kinase in B-CLL is different from the expression of their counterparts in normal B cells [46,51]. Whether this defect is the cause of immune disorders in patients with B-CLL remains to be proven.…”

Section: Resultsmentioning

confidence: 92%

“…Nomura et al [42] showed that LPS stimulation of monocytes leads to the reduction of TLR4 expression. The minimal to undetectable TLR4 expression in CLL cells was observed [46]. It may be caused by chronic stimulation of CLL cells by unknown antigens, environmental factors and cytokines and protein expression.…”

Section: Resultsmentioning

confidence: 99%

Distinct IRAK4 Expression in Normal and B-CLL Lymphocytes

Antosz¹

2014

J Cytol Histol

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Toll-like receptors (TLR) signaling plays an important role in the B cell biology. It induces the maturation, proliferation and antibody production in response to pathogen recognition. Interleukin-1 Receptor-associated Kinase-4 (IRAK-4) is TLR downstream molecule which is of strategic importance in starting a cascade of NF-kappaB (Nuclear factor-kappaB) and MAPK (Mitogen-activated protein kinase) intracellular signaling pathways. The aim of the study was to identify the differences in IRAK-4 expression in normal and chronic lymphocytic leukemia (CLL) lymphocytes. We have also studied the IRAK-4 expression alteration upon TLR2/4 ligand stimulation in leukemic and normal B cells. IRAK-4 mRNA expression was significantly higher in normal CD19+ lymphocytes as compared to leukemic CD5 + CD19+ subpopulation (RQ median 0.90 vs 0.54; p=0.012). In normal lymphocytes, LPS and SAC treatment led to significant IRAK-4 down-regulation both at mRNA (RQ median 0.90 vs 0.53 vs 0.40; p=0.03, p=0.01) and protein level, whereas generally there were no significant changes in IRAK-4 expression neither on mRNA nor protein level.No trend or significant differences in IRAK-4 expression in leukemic lymphocytes after LPS and SAC stimulation may imply the presence of alleged defect of immune tolerance in CLL.

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“…Interestingly, dysregulated TLR2 expression/signaling has been reported in certain B cell lymphomas. 58,59 Investigations elucidating TLRmediated activation in the genesis of non-AIDS-defining B cell malignancies could lead to the development of biomarkers and therapeutic interventions.…”

Section: Fig 2 (Continued)mentioning

confidence: 99%

A Role for TLR Signaling During B Cell Activation in Antiretroviral-Treated HIV Individuals

Siewe

Keshavarzian

French

et al. 2013

AIDS Research and Human Retroviruses

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The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART(+)). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART(+) and HIV(-) subjects. However, B cells of HIVART(+) subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART(+) individuals were less responsive to TLR stimulation compared to B cells of HIV(-) subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV(-) subjects was similar to ex vivo B cells from HIVART(+) individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV(-) subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART(+) subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART(+) subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation.

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TLR2 may influence the behavior of the malignant clone in B-CLL

Cited by 8 publications

References 23 publications

TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia

TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic Leukemia

Distinct IRAK4 Expression in Normal and B-CLL Lymphocytes

A Role for TLR Signaling During B Cell Activation in Antiretroviral-Treated HIV Individuals

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