ArticleNature communications2022
Exploiting endogenous and therapy-induced apoptotic vulnerabilities in immunoglobulin light chain amyloidosis with BH3 mimetics.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Profiling proteomic responses in small intestinal neuroendocrine tumor GOT1 after [BMC cancer · 2026Article
- Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis.Bioactive materials · 2026Article
- Platelet aging and desialylation increase apoptotic priming and BCL-XCell death & disease · 2026Article
- Efficacy of venetoclax in the treatment of relapsed/refractory light-chain amyloidosis.Annals of hematology · 2025Article
- BCL-xL dependency in chromophobe renal cell carcinoma.Cancer gene therapy · 2025Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- Paclitaxel-induced mitotic arrest results in a convergence of apoptotic dependencies that can be safely exploited by BCL-XbioRxiv : the preprint server for biology · 2025Article
- The molecular landscape of AL amyloidosis.British journal of haematology · 2025Review
- Three years follow-up of Venetoclax in advanced-stage, relapsed or refractory AL amyloidosis with cardiac involvement and t(11;14) with BCL2 expression.Annals of hematology · 2024Observational
- Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.British journal of cancer · 2024Article
- In situ architecture of Opa1-dependent mitochondrial cristae remodeling.The EMBO journal · 2024Article
- Article
- Radiotherapy-Induced Neurocognitive Impairment Is Driven by Heightened Apoptotic Priming in Early Life and Prevented by Blocking BAX.Cancer research · 2023Article
- Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study.Cancers · 2023Article
- Endogenous and imposed determinants of apoptotic vulnerabilities in cancer.Trends in cancer · 2023Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Immunoglobulin light chain (AL) amyloidosis is an incurable hematologic disorder typically characterized by the production of amyloidogenic light chains by clonal plasma cells. These light chains misfold and aggregate in healthy tissues as amyloid fibrils, leading to life-threatening multi-organ dysfunction. Here we show that the clonal plasma cells in AL amyloidosis are highly primed to undergo apoptosis and dependent on pro-survival proteins MCL-1 and BCL-2. Notably, this MCL-1 dependency is indirectly targeted by the proteasome inhibitor bortezomib, currently the standard of care for this disease and the related plasma cell disorder multiple myeloma, due to upregulation of pro-apoptotic Noxa and its inhibitory binding to MCL-1. BCL-2 inhibitors sensitize clonal plasma cells to multiple front-line therapies including bortezomib, dexamethasone and lenalidomide. Strikingly, in mice bearing AL amyloidosis cell line xenografts, single agent treatment with the BCL-2 inhibitor ABT-199 (venetoclax) produces deeper remissions than bortezomib and triples median survival. Mass spectrometry-based proteomic analysis reveals rewiring of signaling pathways regulating apoptosis, proliferation and mitochondrial metabolism between isogenic AL amyloidosis and multiple myeloma cells that divergently alter their sensitivity to therapies. These findings provide a roadmap for the use of BH3 mimetics to exploit endogenous and induced apoptotic vulnerabilities in AL amyloidosis.
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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.