ArticleCell death and differentiation2020
Deep profiling of apoptotic pathways with mass cytometry identifies a synergistic drug combination for killing myeloma cells.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
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- Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia.Blood · 2024Article
- Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development.Cancer research · 2024Article
- Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers.Nature cell biology · 2024Article
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- Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells.Blood advances · 2023Article
- To metabolomics and beyond: a technological portfolio to investigate cancer metabolism.Signal transduction and targeted therapy · 2023Review
- Review
- Heterogeneity of B cell lymphopoiesis in patients with premalignant and active myeloma.JCI insight · 2023Article
- Exploiting endogenous and therapy-induced apoptotic vulnerabilities in immunoglobulin light chain amyloidosis with BH3 mimetics.Nature communications · 2022Article
- Hybrid Fluorescent Mass-Tag Nanotrackers as Universal Reagents for Long-Term Live-Cell Barcoding.Analytical chemistry · 2022Article
- Machine Learning and Deep Learning Applications in Multiple Myeloma Diagnosis, Prognosis, and Treatment Selection.Cancers · 2022Review
- treekoR: identifying cellular-to-phenotype associations by elucidating hierarchical relationships in high-dimensional cytometry data.Genome biology · 2021Article
- Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer.Discover oncology · 2021Review
- Making the most of high-dimensional cytometry data.Immunology and cell biology · 2021Review
- Direct P70S6K1 inhibition to replace dexamethasone in synergistic combination with MCL-1 inhibition in multiple myeloma.Blood advances · 2021Article
- Extended live-cell barcoding approach for multiplexed mass cytometry.Scientific reports · 2021Article
- Targeted Therapies for Multiple Myeloma.Journal of personalized medicine · 2021Review
- Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Multiple myeloma is an incurable and fatal cancer of immunoglobulin-secreting plasma cells. Most conventional therapies aim to induce apoptosis in myeloma cells but resistance to these drugs often arises and drives relapse. In this study, we sought to identify the best adjunct targets to kill myeloma cells resistant to conventional therapies using deep profiling by mass cytometry (CyTOF). We validated probes to simultaneously detect 26 regulators of cell death, mitosis, cell signaling, and cancer-related pathways at the single-cell level following treatment of myeloma cells with dexamethasone or bortezomib. Time-resolved visualization algorithms and machine learning random forest models (RFMs) delineated putative cell death trajectories and a hierarchy of parameters that specified myeloma cell survival versus apoptosis following treatment. Among these parameters, increased amounts of phosphorylated cAMP response element-binding protein (CREB) and the pro-survival protein, MCL-1, were defining features of cells surviving drug treatment. Importantly, the RFM prediction that the combination of an MCL-1 inhibitor with dexamethasone would elicit potent, synergistic killing of myeloma cells was validated in other cell lines, in vivo preclinical models and primary myeloma samples from patients. Furthermore, CyTOF analysis of patient bone marrow cells clearly identified myeloma cells and their key cell survival features. This study demonstrates the utility of CyTOF profiling at the single-cell level to identify clinically relevant drug combinations and tracking of patient responses for future clinical trials.
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Registered trials
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