ArticleLeukemia2020
Bidirectional linkage between the B-cell receptor and NOTCH1 in chronic lymphocytic leukemia and in Richter's syndrome: therapeutic implications.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Functional cooperation between the B-cell receptor and NOTCH1 in regulating metabolic reprogramming in chronic lymphocytic leukemia.Leukemia · 2026Article
- Article
- Molecular Features Accompanying Richter's Transformation in Patients with Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Review
- Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications.Frontiers in oncology · 2024Review
- The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy.Haematologica · 2023Article
- Editorial: The notch signaling pathway in lymphoid malignancies.Frontiers in oncology · 2023Article
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.Cell death & disease · 2022Article
- An Approach to Diagnosis of Richter Transformation in Chronic Lymphocytic Leukemia.Journal of the advanced practitioner in oncology · 2022Article
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- Review
- Review
- Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets.Cancers · 2021Review
- Non-Coding RNAs: The "Dark Side Matter" of the CLL Universe.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.iScience · 2021Article
- NOTCH1 Activation Negatively Impacts on Chronic Lymphocytic Leukemia Outcome and Is Not Correlated to theFrontiers in oncology · 2021Article
- Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies.Haematologica · 2020Review
- Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
NOTCH1 mutations in chronic lymphocytic leukemia (CLL) lead to accumulation of NOTCH1 intracellular domain (NICD) and prolong signaling. These mutations associate with a more aggressive disease compared to wild-type (WT) CLL. In this work we demonstrate a bidirectional functional relationship between NOTCH1 and the B cell receptor (BCR) pathways. By using highly homogeneous cohorts of primary CLL cells, activation of NOTCH1 is shown to increase expression of surface IgM, as well as LYN, BTK, and BLNK, ultimately enhancing BCR signaling responses, including global mRNA translation. Upon BCR cross-linking, NOTCH1 itself is actively translated and increased on cell surface. Furthermore, BCR ligation induces calcium mobilization that can facilitate ligand-independent NOTCH1 activation. These data suggest that the two pathways are functionally linked, providing a rationale for dual inhibition strategies. Consistently, addition of the γ-secretase inhibitor DAPT to ibrutinib significantly potentiates its effects, both in vitro and in a short-term patient-derived xenograft model. While this observation may find limited applications in the CLL field, it is more relevant for Richter's Syndrome (RS) management, where very few successful therapeutic options exist. Treatment of RS-patient-derived xenografts (RS-PDX) with the combination of ibrutinib and DAPT decreases disease burden and increases overall survival.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.