ArticleBritish journal of haematology2014
AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia.
Article in British journal of haematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Prognostic value of fatty acid metabolism-related signature and integrated analysis of the immune microenvironment in multiple myeloma.BMC cancer · 2025Article
- Targeting BCL2 in Waldenström macroglobulinemia: from biology to treatment management.Frontiers in oncology · 2025Review
- Review
- PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy.Cell reports. Medicine · 2023Article
- Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma.Blood advances · 2023Article
- AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.Cancers · 2023Article
- Updates in the Use of BCL-2-Family Small Molecule Inhibitors for the Treatment of Relapsed/Refractory Multiple Myeloma.Cancers · 2022Review
- Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen dysregulates expression of MCL-1 by targeting FBW7.PLoS pathogens · 2021Article
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Clinical Review: Navitoclax as a Pro-Apoptotic and Anti-Fibrotic Agent.Frontiers in pharmacology · 2020Review
- Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Targeting Bcl-2 for the treatment of multiple myeloma.Leukemia · 2018Review
- Proteasome-associated deubiquitinases and cancer.Cancer metastasis reviews · 2017Review
- Waldenstrom macroglobulinemia cells devoid of BTKBlood cancer journal · 2017Article
- Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.Blood cancer journal · 2016Article
- Targeted inhibition of the deubiquitinating enzymes, USP14 and UCHL5, induces proteotoxic stress and apoptosis in Waldenström macroglobulinaemia tumour cells.British journal of haematology · 2015Article
- Article
- Imaging cellular distribution of Bcl inhibitors using small molecule drug conjugates.Bioconjugate chemistry · 2014Article
- Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia.Blood cancer journal · 2014Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti-tumour effects of a pan-BCL2 inhibitor, AT-101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenström macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT-101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase-dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT-101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA-treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT-101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy.
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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.