ArticleLeukemia2014
Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.Blood cancer journal · 2024Trial
- Trial
- Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma.Annals of hematology · 2020Trial
- Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis.Leukemia · 2019Trial
- Trial
- Trial
- The Spectrum and Clinical Impact of Epigenetic Modifier Mutations in Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Trial
- Trial
- Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.Journal of translational medicine · 2026Review
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.PloS one · 2026Article
- Single mutation tunes IRF4 function and mediates B cell character to ameliorate murine lupus.iScience · 2025Article
- [Value of gene mutation in the prognosis and treatment of multiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- Clinical implications of ctDNA-based minimal residual disease detection in newly diagnosed peripheral T-cell lymphoma: a single-center cohort study.Cell communication and signaling : CCS · 2025Article
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.bioRxiv : the preprint server for biology · 2025Article
- Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.Journal of translational medicine · 2025Article
- Review
- Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?Annals of hematology · 2025Review
- Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression.Cancer research communications · 2025Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ(null) xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.
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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.