ArticleBlood2021
Active Akt signaling triggers CLL toward Richter transformation via overactivation of Notch1.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 87 citations in OpenAlex.
- Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial.Nature medicine · 2024Trial
- Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis.Developmental cell · 2026Article
- CD49d governs immune synapse formation through actin rearrangements and synchronizes BCR signaling in CLL.Blood · 2026Article
- Functional cooperation between the B-cell receptor and NOTCH1 in regulating metabolic reprogramming in chronic lymphocytic leukemia.Leukemia · 2026Article
- Prolymphocytic Progression in Chronic Lymphocytic Leukemia Without Richter Transformation: An Eighteen-Year Clinical-Diagnostic Correlation.Case reports in hematology · 2026Article
- Evaluation of the Role of AID-Induced Mutagenesis in Resistance to B-Cell Receptor Pathway Inhibitors in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Article
- Richter's transformation: status quo and quo vadis.Annals of hematology · 2025Review
- Tonic signaling of the B-cell antigen-specific receptor is a common functional hallmark in chronic lymphocytic leukemia cell phosphoproteomes at early disease stages.Molecular oncology · 2025Article
- Eμ-TCL1 mice with conditional human BCL2 knockin as novel B-cell lymphoma model for studying venetoclax effects in vivo.Blood neoplasia · 2025Article
- Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia.FEBS letters · 2025Review
- CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies.Science advances · 2025Article
- Effect of statins on IL-10 signaling and production by chronic lymphocytic leukemia cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Bruton tyrosine kinase covalent inhibition shapes the immune microenvironment in chronic lymphocytic leukemia.Haematologica · 2025Article
- Molecular Features Accompanying Richter's Transformation in Patients with Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Review
- Bcor loss promotes Richter transformation of chronic lymphocytic leukemia associated with Notch1 activation in mice.Leukemia · 2025Article
- Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies.Cancers · 2025Review
- A question of TiME: how microenvironmental interactions shape response to immunotherapy in CLL and Richter Transformation.Frontiers in immunology · 2025Review
- Proliferating CLL cells express high levels of CXCR4 and CD5.HemaSphere · 2024Article
- Article
- Multiple omics levels of chronic lymphocytic leukemia.Cell death discovery · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Richter's transformation (RT) is an aggressive lymphoma that occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL phase involving TP53, CDKN2A, MYC, and NOTCH1; however, a significant proportion of RT cases lack CLL phase-associated events. Here, we report that high levels of AKT phosphorylation occur both in high-risk CLL patients harboring TP53 and NOTCH1 mutations as well as in patients with RT. Genetic overactivation of Akt in the murine Eµ-TCL1 CLL mouse model resulted in CLL transformation to RT with significantly reduced survival and an aggressive lymphoma phenotype. In the absence of recurrent mutations, we identified a profile of genomic aberrations intermediate between CLL and diffuse large B-cell lymphoma. Multiomics assessment by phosphoproteomic/proteomic and single-cell transcriptomic profiles of this Akt-induced murine RT revealed an S100 protein-defined subcluster of highly aggressive lymphoma cells that developed from CLL cells, through activation of Notch via Notch ligand expressed by T cells. Constitutively active Notch1 similarly induced RT of murine CLL. We identify Akt activation as an initiator of CLL transformation toward aggressive lymphoma by inducing Notch signaling between RT cells and microenvironmental T cells.
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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 OpenQuestion graph.