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Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response
by
Rodríguez-Perales, Sandra
, Horcajo, Beatriz
, Garcia-Grande, Aranzazu
, Sánchez-Beato, Margarita
, Pedrosa, Lucía
, Pérez-Aguilera, Marina
, Gómez, Sagrario
, Torres-Ruiz, Raúl
, Muñoz-Viana, Rafael
, Yanguas-Casás, Natalia
, Fernández-Miranda, Ismael
in
631/337
/ 631/67
/ 631/80
/ 692/4028
/ B-cell lymphoma
/ Cell activation
/ Cell Line, Tumor
/ Cell migration
/ Cell morphology
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Cell survival
/ Cells
/ CRISPR
/ CRISPR-Cas Systems
/ Disease
/ Genes
/ Germinal centers
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ Lymphocytes B
/ Lymphoma
/ Lymphoma, B-Cell - drug therapy
/ Lymphoma, B-Cell - genetics
/ Lymphoma, B-Cell - pathology
/ Medical prognosis
/ multidisciplinary
/ Mutation
/ Oxidative metabolism
/ Oxidative phosphorylation
/ Peptides
/ Physiology
/ Point Mutation
/ Polyethylene glycol
/ RNA Splice Sites - genetics
/ Science
/ Science (multidisciplinary)
/ Therapeutic targets
/ Trans-Activators - genetics
/ Transcription factors
/ Tumor cell lines
2026
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Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response
by
Rodríguez-Perales, Sandra
, Horcajo, Beatriz
, Garcia-Grande, Aranzazu
, Sánchez-Beato, Margarita
, Pedrosa, Lucía
, Pérez-Aguilera, Marina
, Gómez, Sagrario
, Torres-Ruiz, Raúl
, Muñoz-Viana, Rafael
, Yanguas-Casás, Natalia
, Fernández-Miranda, Ismael
in
631/337
/ 631/67
/ 631/80
/ 692/4028
/ B-cell lymphoma
/ Cell activation
/ Cell Line, Tumor
/ Cell migration
/ Cell morphology
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Cell survival
/ Cells
/ CRISPR
/ CRISPR-Cas Systems
/ Disease
/ Genes
/ Germinal centers
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ Lymphocytes B
/ Lymphoma
/ Lymphoma, B-Cell - drug therapy
/ Lymphoma, B-Cell - genetics
/ Lymphoma, B-Cell - pathology
/ Medical prognosis
/ multidisciplinary
/ Mutation
/ Oxidative metabolism
/ Oxidative phosphorylation
/ Peptides
/ Physiology
/ Point Mutation
/ Polyethylene glycol
/ RNA Splice Sites - genetics
/ Science
/ Science (multidisciplinary)
/ Therapeutic targets
/ Trans-Activators - genetics
/ Transcription factors
/ Tumor cell lines
2026
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Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response
by
Rodríguez-Perales, Sandra
, Horcajo, Beatriz
, Garcia-Grande, Aranzazu
, Sánchez-Beato, Margarita
, Pedrosa, Lucía
, Pérez-Aguilera, Marina
, Gómez, Sagrario
, Torres-Ruiz, Raúl
, Muñoz-Viana, Rafael
, Yanguas-Casás, Natalia
, Fernández-Miranda, Ismael
in
631/337
/ 631/67
/ 631/80
/ 692/4028
/ B-cell lymphoma
/ Cell activation
/ Cell Line, Tumor
/ Cell migration
/ Cell morphology
/ Cell Movement - genetics
/ Cell proliferation
/ Cell Proliferation - genetics
/ Cell survival
/ Cells
/ CRISPR
/ CRISPR-Cas Systems
/ Disease
/ Genes
/ Germinal centers
/ Humanities and Social Sciences
/ Humans
/ Invasiveness
/ Lymphocytes B
/ Lymphoma
/ Lymphoma, B-Cell - drug therapy
/ Lymphoma, B-Cell - genetics
/ Lymphoma, B-Cell - pathology
/ Medical prognosis
/ multidisciplinary
/ Mutation
/ Oxidative metabolism
/ Oxidative phosphorylation
/ Peptides
/ Physiology
/ Point Mutation
/ Polyethylene glycol
/ RNA Splice Sites - genetics
/ Science
/ Science (multidisciplinary)
/ Therapeutic targets
/ Trans-Activators - genetics
/ Transcription factors
/ Tumor cell lines
2026
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Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response
Journal Article
Splice-site mutations in POU2AF1 are associated with B-cell lymphomagenesis and therapeutic response
2026
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Overview
BOB.1, encoded by
POU2AF1
, is one of many factors regulating physiological B-cell maturation in the germinal center. Recently, several studies have described recurrent mutations in a three-nucleotide region in the
POU2AF1
splice site in the two most common B-cell non-Hodgkin lymphomas: diffuse large B-cell lymphoma and, more frequently, follicular lymphoma. In this study, we introduced a C→G mutation at the + 1 position of the
POU2AF1
splice site in two B-cell lymphoma cell lines (WSU-NHL and SUDHL4) using CRISPR/Cas9 gene editing. Our results demonstrate how point mutations in the
POU2AF1
splice site decreased BOB.1 expression levels. The mutation did not produce significant changes in cell proliferation, migration, or invasiveness, but did affect cell morphology, aggregation, and cell survival in a cell-line-dependent manner. Lastly, we found that the
POU2AF1
mutation c.16 + 1G > C increased BCR activation, especially in SUDHL4 cells, downregulated oxidative phosphorylation (OxPhos) metabolism, and modified therapy sensitivities in both cell lines. Mutated B-cells were more sensitive to the BTK inhibitor ibrutinib. In conclusion, mutations in the
POU2AF1
splice site impact B-cell lymphomagenesis at multiple levels and represent a potential therapeutic target for patients with tumors harboring this mutation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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