ArticlePloS one2011
Differentiation of chronic lymphocytic leukemia B cells into immunoglobulin secreting cells decreases LEF-1 expression.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- RNA NExperimental & molecular medicine · 2025Article
- Oncotherapy resistance explained by Darwinian and Lamarckian models.The Journal of clinical investigation · 2024Article
- Relevance of Additional Immunohistochemical Markers in the Differential Diagnosis of Small B-Cell Lymphomas: A Case-Control StudyTurkish journal of haematology : official journal of Turkish Society of Haematology · 2022Article
- Immunohistochemistry Innovations for Diagnosis and Tissue-Based Biomarker Detection.Current hematologic malignancy reports · 2019Review
- Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia.Oncotarget · 2019Article
- Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective.Frontiers in immunology · 2018Review
- Wnt signalling pathways in chronic lymphocytic leukaemia and B-cell lymphomas.British journal of pharmacology · 2017Review
- Toll-like receptor 9 stimulation can induce IκBζ expression and IgM secretion in chronic lymphocytic leukemia cells.Haematologica · 2017Article
- Chronic lymphocytic leukemia cells diversify and differentiate in vivo via a nonclassical Th1-dependent, Bcl-6-deficient process.JCI insight · 2016Article
- The many faces of small B cell lymphomas with plasmacytic differentiation and the contribution of MYD88 testing.Virchows Archiv : an international journal of pathology · 2016Review
- Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells.Oncotarget · 2015Article
- Chronic lymphocytic leukaemia: could immunological tolerance mechanisms be the origin of lymphoid neoplasms?Immunology · 2014Review
- TLR9 Ligand (CpG Oligodeoxynucleotide) Induces CLL B-Cells to Differentiate into CD20(+) Antibody-Secreting Cells.Frontiers in immunology · 2014Article
- Chronic lymphocytic leukemia: molecular heterogeneity revealed by high-throughput genomics.Genome medicine · 2013Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Lymphocyte enhancer binding factor 1 (LEF-1) plays a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia (CLL) cells aberrantly express LEF-1 and its expression is required for cellular survival. We hypothesized that modification of the differentiation status of CLL cells would result in loss of LEF-1 expression and eliminate the survival advantage provided by its aberrant expression. In this study, we first established a methodology that induces CLL cells to differentiate into immunoglobulin (Ig) secreting cells (ISC) using the TLR9 agonist, CpG, together with cytokines (CpG/c). CpG/c stimulation resulted in dramatic CLL cell phenotypic and morphologic changes, expression of cytoplasmic Ig, and secretion of light chain restricted Ig. CpG/c stimulation also resulted in decreased CLL cell LEF-1 expression and increased Blimp-1 expression, which is crucial for plasma cell differentiation. Further, Wnt pathway activation and cellular survival were impaired in differentiated CLL cells compared to undifferentiated CLL cells. These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation.
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