B-cell receptor signaling in the pathogenesis of lymphoid malignancies

Bojarczuk, Kamil; Bobrowicz, Małgorzata; Dwojak, Michal; Miązek, Nina; Zapała, Piotr; Bunes, Anders; Siernicka, Marta; Różańska, M.; Winiarska, Magdalena

doi:10.1016/j.bcmd.2015.06.016

Cited by 25 publications

(26 citation statements)

References 148 publications

(117 reference statements)

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“…We first investigated aptamer specificity by analyzing the binding of individual fluorescently labeled aptamers with Jurkat.E6, using Burkitt’s lymphoma cell line Ramos as the negative control cell line. Burkitt’s lymphoma, which is from the B-cell lineage, does not express TCR-CD3 complex; therefore, sequences that do not bind to Ramos cells would be specific for TCR complex 13 . Interestingly, out of 27 tested sequences (Supporting Information; Figure S3), three sequences, J4, J7 and J14, showed specificity against Jurkat.E6 cells, but not control Ramos cells.…”

Section: Resultsmentioning

confidence: 99%

Ligand-guided selection of aptamers against T-cell Receptor-cluster of differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells

Zumrut

Ara

Maio

et al. 2016

Analytical Biochemistry

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We recently introduced a screening technology termed ligand-guided selection, (LIGS), to selectively identify target-specific aptamers from an evolved cell-SELEX library. Cell-SELEX utilizes a large combinatorial single-stranded oligonucleotide library and progressively selects DNA ligands against whole cells with variable DNA-binding affinities and specificities by repeated rounds of partition and amplification. LIGS exploits the partition step and introduces a secondary, pre-existing high-affinity monoclonal antibody (mAb) ligand to outcompete and elute specific aptamers towards the binding target of the antibody, not the cell. Here, using anti-CD3ε mAb against the cluster of differentiation 3 (CD3ε), as the guiding ligand against one of the domains of the T-Cell Receptor (TCR) complex expressed on Jurkat.E6 cells, we discovered three specific aptamers against TCR complex expressed on an immortalized line of human T lymphocyte cells. In sum, we demonstrate that specific aptamers can be identified utilizing an antibody against a single domain of a multidomain protein complex in their endogenous state with neither post- nor pre-SELEX protein manipulation.

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Section: Resultsmentioning

confidence: 99%

Ligand-guided selection of aptamers against T-cell Receptor-cluster of differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells

Zumrut

Ara

Maio

et al. 2016

Analytical Biochemistry

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Section: Resultsmentioning

confidence: 99%

“…Also, mIgM plays a major role in autoimmune disorders and 95% of human lymphomas originate from B-cells [24][25][26]. There is evidence of activated protein kinase stimulated downstream of B-cell receptor (BCR), demonstrating the significance of developing therapeutics against BCR [24][25][26]. Currently, there are no successful targeting agents available 1 (b).…”

Section: Resultsmentioning

confidence: 99%

“…The mIgM molecule is considered the hallmark of B-cells, plays a major role in B-cell development, and is a major player in transformation of B-cells into malignant B-cells [24][25][26]. Also, mIgM plays a major role in autoimmune disorders and 95% of human lymphomas originate from B-cells [24][25][26]. There is evidence of activated protein kinase stimulated downstream of B-cell receptor (BCR), demonstrating the significance of developing therapeutics against BCR [24][25][26].…”

Section: Resultsmentioning

confidence: 99%

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Ligand-Guided Selection of Target-Specific Aptamers: A Screening Technology for Identifying Specific Aptamers Against Cell-Surface Proteins

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Ara

Fraile

et al. 2016

Nucleic Acid Therapeutics

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We report on a new strategy for identifying highly specific aptamers against a predetermined epitope of a target. Termed ''ligand-guided selection'' (LIGS), this method uniquely exploits the selection step, the core of SELEX (Systematic Evolution Exponential enrichment). LIGS uses a naturally occurring stronger and highly specific bivalent binder, an antibody (Ab) interacting with its cognate antigen to outcompete specific aptamers from a partially enriched SELEX pool, as a strategy. We demonstrate the hypothesis of LIGS by utilizing an Ab binding to membrane-bound Immunoglobulin M (mIgM) to selectively elute aptamers that are specific for mIgM from a SELEX pool that is partially enriched toward mIgM expressing Ramos cells. The selected aptamers show specificity toward Ramos cells. We identified three aptamer candidates utilizing LIGS that could be outcompeted by mIgM Ab, demonstrating that LIGS can be successfully applied to select aptamers from a partially evolved cell-SELEX library, against predetermined receptor proteins using a cognate ligand. This proof-of-concept study introduces a new biochemical-screening platform that exploits the binding of a secondary stronger molecular entity to its target as a partition step, to identify highly specific artificial nucleic acid ligands.

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“…The signal is propagated downstream of the BCR through a series of kinases, including the LYN, spleen tyrosine kinase (SYK), and BTK kinases, ultimately activating transcriptional programs in the nucleus that regulate B-cell function. [23][24][25] More than 100 clinical trials of ibrutinib are ongoing in an effort to further clarify its role in a variety of different disease settings. Furthermore, in an effort to address some of the toxicity concerns with ibrutinib, more specific BTK inhibitors are also being developed.…”

Section: B-cell Signaling a Ripe Targetmentioning

confidence: 99%

Immunotherapies shape the treatment landscape for hematologic malignancies

Lartigue¹

2017

J Community Support Oncology

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B-cell receptor signaling in the pathogenesis of lymphoid malignancies

Cited by 25 publications

References 148 publications

Ligand-guided selection of aptamers against T-cell Receptor-cluster of differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells

Ligand-guided selection of aptamers against T-cell Receptor-cluster of differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells

Ligand-Guided Selection of Target-Specific Aptamers: A Screening Technology for Identifying Specific Aptamers Against Cell-Surface Proteins

Immunotherapies shape the treatment landscape for hematologic malignancies

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