ArticleCell reports2019
Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions.Cellular & molecular immunology · 2025Article
- Towards a unifying model for B-cell receptor triggering.Nature reviews. Immunology · 2025Review
- Human TCR repertoire in cancer.Cancer medicine · 2024Review
- StellarPath: Hierarchical-vertical multi-omics classifier synergizes stable markers and interpretable similarity networks for patient profiling.PLoS computational biology · 2024Article
- ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia.Blood advances · 2024Article
- Dynamic hydrogen peroxide levels reveal a rate-dependent sensitivity in B-cell lymphoma signaling.Scientific reports · 2024Article
- Phosphatidylserine synthesis controls oncogenic B cell receptor signaling in B cell lymphoma.The Journal of cell biology · 2024Article
- In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival.HemaSphere · 2023Article
- Rheumatoid factor IgM autoantibodies control IgG homeostasis.Frontiers in immunology · 2022Article
- Spatial organization and early signaling of the B-cell receptor in CLL.Frontiers in immunology · 2022Article
- The Determinants of B Cell Receptor Signaling as Prototype Molecular Biomarkers of Leukemia.Frontiers in oncology · 2021Article
- Modeling immune cell behavior across scales in cancer.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
In cancer biology, the functional interpretation of genomic alterations is critical to achieve the promise of genomic profiling in the clinic. For chronic lymphocytic leukemia (CLL), a heterogeneous disease of B-lymphocytes maturing under constitutive B cell receptor (BCR) stimulation, the functional role of diverse clonal mutations remains largely unknown. Here, we demonstrate that alterations in BCR signaling dynamics underlie the progression of B cells toward malignancy. We reveal emergent dynamic features-bimodality, hypersensitivity, and hysteresis-in the BCR signaling pathway of primary CLL B cells. These signaling abnormalities in CLL quantitatively derive from BCR clustering and constitutive signaling with positive feedback reinforcement, as demonstrated through single-cell analysis of phospho-responses, computational modeling, and super-resolution imaging. Such dysregulated signaling segregates CLL patients by disease severity and clinical presentation. These findings provide a quantitative framework and methodology to assess complex and heterogeneous leukemia pathology and to inform therapeutic strategies in parallel with genomic profiling.
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