scholarly journals Complementarity determining region-independent recognition of a superantigen by B-cell antigen receptors of mantle cell lymphoma

Haematologica ◽  
2016 ◽  
Vol 101 (9) ◽  
pp. e378-e381 ◽  
Author(s):  
M. Fichtner ◽  
E. Spies ◽  
H. Seismann ◽  
K. Riecken ◽  
N. Engels ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Antigen Receptors ◽  
Cell Antigen ◽  
Mantle Cell ◽  
Complementarity Determining Region

scholarly journals The role of B cell antigen receptors in mantle cell lymphoma

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Michael Fichtner ◽  
Martin Dreyling ◽  
Mascha Binder ◽  
Martin Trepel
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Antigen Receptors ◽  
Cell Antigen ◽  
Mantle Cell

TLR-9 and B-Cell Antigen Receptor Triggering of Primary B Cells From Mantle Cell Lymphoma Induce Cell Proliferation and Telomerase Activity,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3690-3690
Author(s):  
Sonal Temburni ◽  
Ryon M. Andersen ◽  
Steven L. Allen ◽  
Jaqueline C. Barrientos ◽  
Jonathan E. Kolitz ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Telomerase Activity ◽  
B Cell Antigen Receptor ◽  
Cell Antigen ◽  
Mantle Cell ◽  
T Cell Help

Abstract Abstract 3690 Mantle cell lymphoma (MCL), a less common non-Hodgkin's lymphoma (NHL), often has a poor prognosis and a median survival time of 3–5 years. Historically, MCLs were believed to originate from mature but naive B cells; this notion has now changed based on the demonstration of somatically mutated IgHV sequences in the lymphoma cells from a subset of cases. Indirect evidence suggesting that the B-cell receptor (BCR) pathway may be at the base of the observed activation in the disease exists; however, that extent that this activation results from Toll-like receptor (TLR), B-cell antigen receptor (BCR), or a combination of signaling from both has not been adequately addressed. In this study, the responsiveness of purified primary B cells isolated from peripheral blood (PB) and/or bone marrow (BM) of MCL patients in the leukemic phase of the disease to triggering via the BCR or via TLR-9 alone or in context with selected chemokines – CCL17, CCL22, or CXCL12 - was assessed using various early and late cell signaling readouts. Phosphoflow analysis revealed that within 5 minutes of stimulation both PB and BM B cells significantly increased levels of pAkt and pNFkB in response to BCR crosslinking by an anti-IgM monoclonal antibody (mAb). When PB B cells were cultured for 3 days in the presence of various stimuli to evaluate their proliferative response (uptake of 3H-thymidine), anti-BCR triggering stimulated 2 to 5.5 fold increases in DNA synthesis, whereas the TLR-9 agonist ODN2006 elicited 55 to 235 fold increases. In addition, conditions simulating T-cell help (anti-CD40 mAb + IL-4 in the presence of CD32-transfected fibroblasts) stimulated significant (40–65 fold) proliferative responses in MCL B cells. Simultaneously, a significant increase in HLA-DR (anti-BCR: 49%; ODN2006: 61%; T-cell help: 20%) and Bcl-2 expression (anti-BCR: 21%; ODN2006: 36%; T-cell help: 25%) was induced by these stimuli. Furthermore, B cells from the BM of the same cases differed in their proliferative responses based on the agonist. Thus, in response to BCR triggering, B cells from BM proliferated to a greater extent compared with PB B cells, whereas in response to TLR-9 stimulation PB B cells proliferated to a greater extent than those from BM. In independent experiments, B cells were incubated with various stimuli including those simulating T-cell help and chemokines for 3 days. Cells were harvested and extracts prepared from viable cells to determine telomerase activity using the telomere repeat amplification protocol (TRAP). Anti-BCR stimulation and anti-TLR-9 stimulation independently increased telomerase activity 1.7 and 1.9 fold, respectively, whereas in combination with CCL17 and CCL22, anti-TLR-9 stimulation further increased telomerase activity to 2.28 and 2.36 fold, respectively. In summary, these findings suggest an important role for commonly encountered microenvironmental influences interacting with TLR9 and to a lesser extent the BCR in promoting the aggressiveness of MCL. They also suggest that responses to these stimuli differ between MCL cells residing in the BM and those circulating in the blood. Finally, the data suggest that ligands for CCR4 may play an enhancing role for signals transduced by the BCR and TLR-9 in this disease. If documented in a larger number of cases, treatment regimens that target these signaling pathways might be of therapeutic value. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The B-cell tumor–associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4532-4541 ◽  
Author(s):  
Michael Hudecek ◽  
Thomas M. Schmitt ◽  
Sivasubramanian Baskar ◽  
Maria Teresa Lupo-Stanghellini ◽  
Tetsuya Nishida ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Chimeric Antigen Receptor ◽  
Cell Lymphoma ◽  
Embryonic Stem ◽  
Antigen Receptor ◽  
Orphan Receptor ◽  
Mantle Cell

Monoclonal antibodies and T cells modified to express chimeric antigen receptors specific for B-cell lineage surface molecules such as CD20 exert antitumor activity in B-cell malignancies, but deplete normal B cells. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) was identified as a highly expressed gene in B-cell chronic lymphocytic leukemia (B-CLL), but not normal B cells, suggesting it may serve as a tumor-specific target for therapy. We analyzed ROR1-expression in normal nonhematopoietic and hematopoietic cells including B-cell precursors, and in hematopoietic malignancies. ROR1 has characteristics of an oncofetal gene and is expressed in undifferentiated embryonic stem cells, B-CLL and mantle cell lymphoma, but not in major adult tissues apart from low levels in adipose tissue and at an early stage of B-cell development. We constructed a ROR1-specific chimeric antigen receptor that when expressed in T cells from healthy donors or CLL patients conferred specific recognition of primary B-CLL and mantle cell lymphoma, including rare drug effluxing chemotherapy resistant tumor cells that have been implicated in maintaining the malignancy, but not mature normal B cells. T-cell therapies targeting ROR1 may be effective in B-CLL and other ROR1-positive tumors. However, the expression of ROR1 on some normal tissues suggests the potential for toxi-city to subsets of normal cells.

Diagnostic utility of SOX11 immunohistochemistry in differentiating cutaneous spread of mantle cell lymphoma from primary cutaneous B-cell lymphomas

2016 ◽  
Vol 43 (4) ◽  
pp. 354-361 ◽  
Author(s):  
Andy C. Hsi ◽  
M. Yadira Hurley ◽  
Sena J. Lee ◽  
Ilana S. Rosman ◽  
Xiaofan Pang ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Diagnostic Utility ◽  
B Cell Lymphomas ◽  
Mantle Cell

scholarly journals Artificial Intelligence Analysis of Gene Expression Predicted the Overall Survival of Mantle Cell Lymphoma and a Large Pan-Cancer Series

Healthcare ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Joaquim Carreras ◽  
Naoya Nakamura ◽  
Rifat Hamoudi
Keyword(s):  
Artificial Intelligence ◽  
Overall Survival ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Accuracy ◽  
Gene Set Enrichment Analysis ◽  
Intelligence Analysis ◽  
Mantle Cell ◽  
Pan Cancer

Mantle cell lymphoma (MCL) is a subtype of mature B-cell non-Hodgkin lymphoma characterized by a poor prognosis. First, we analyzed a series of 123 cases (GSE93291). An algorithm using multilayer perceptron artificial neural network, radial basis function, gene set enrichment analysis (GSEA), and conventional statistics, correlated 20,862 genes with 28 MCL prognostic genes for dimensionality reduction, to predict the patients’ overall survival and highlight new markers. As a result, 58 genes predicted survival with high accuracy (area under the curve = 0.9). Further reduction identified 10 genes: KIF18A, YBX3, PEMT, GCNA, and POGLUT3 that associated with a poor survival; and SELENOP, AMOTL2, IGFBP7, KCTD12, and ADGRG2 with a favorable survival. Correlation with the proliferation index (Ki67) was also made. Interestingly, these genes, which were related to cell cycle, apoptosis, and metabolism, also predicted the survival of diffuse large B-cell lymphoma (GSE10846, n = 414), and a pan-cancer series of The Cancer Genome Atlas (TCGA, n = 7289), which included the most relevant cancers (lung, breast, colorectal, prostate, stomach, liver, etcetera). Secondly, survival was predicted using 10 oncology panels (transcriptome, cancer progression and pathways, metabolic pathways, immuno-oncology, and host response), and TYMS was highlighted. Finally, using machine learning, C5 tree and Bayesian network had the highest accuracy for prediction and correlation with the LLMPP MCL35 proliferation assay and RGS1 was made. In conclusion, artificial intelligence analysis predicted the overall survival of MCL with high accuracy, and highlighted genes that predicted the survival of a large pan-cancer series.

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