ArticleBlood2012
Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 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
203 citing papers in PubMed, 1 synthesis or guideline pooled it, 404 citations in OpenAlex.
- European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma.Haematologica · 2014Guideline
- Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.Blood advances · 2021Trial
- An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics.Blood cancer journal · 2020Trial
- Genomic discovery and clonal tracking in multiple myeloma by cell-free DNA sequencing.Leukemia · 2018Trial
- Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma.Blood advances · 2018Trial
- Circulating tumour DNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates.Nature communications · 2017Trial
- Trial
- A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma.JAMA oncology · 2015Trial
- Whole-exome sequencing of primary plasma cell leukemia discloses heterogeneous mutational patterns.Oncotarget · 2015Trial
- Quantification of clonal circulating plasma cells in relapsed multiple myeloma.British journal of haematology · 2014Trial
- The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine.Trials · 2014Trial
- Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy.Blood · 2014Trial
- The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D.Leukemia · 2026Article
- Research Progress on the Functional Regulation Mechanisms of ZKSCAN3.Biomolecules · 2025Review
- Beyond the bone marrow: a review of therapeutic approaches for extramedullary disease in multiple myeloma and the significance of MRD assessment.Journal of medicine and life · 2025Review
- Clinical Implications of Circulating Tumor DNA in Multiple Myeloma and Its Precursor Diseases.Annals of laboratory medicine · 2025Article
- Article
- Strategies for the drug development of cancer therapeutics.Frontiers in pharmacology · 2025Review
- MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma: a preliminary study.Frontiers in pharmacology · 2025Article
143 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The longitudinal evolution of a myeloma genome from diagnosis to plasma cell leukemia has not previously been reported. We used whole-genome sequencing (WGS) on 4 purified tumor samples and patient germline DNA drawn over a 5-year period in a t(4;14) multiple myeloma patient. Tumor samples were acquired at diagnosis, first relapse, second relapse, and end-stage secondary plasma cell leukemia (sPCL). In addition to the t(4;14), all tumor time points also shared 10 common single-nucleotide variants (SNVs) on WGS comprising shared initiating events. Interestingly, we observed genomic sequence variants that waxed and waned with time in progressive tumors, suggesting the presence of multiple independent, yet related, clones at diagnosis that rose and fell in dominance. Five newly acquired SNVs, including truncating mutations of RB1 and ZKSCAN3, were observed only in the final sPCL sample suggesting leukemic transformation events. This longitudinal WGS characterization of the natural history of a high-risk myeloma patient demonstrated tumor heterogeneity at diagnosis with shifting dominance of tumor clones over time and has also identified potential mutations contributing to myelomagenesis as well as transformation from myeloma to overt extramedullary disease such as sPCL.
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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.