ArticleBlood2023
The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Guideline
- Distinct patient, tumour and chimeric antigen receptor T-cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma.British journal of haematology · 2025Trial
- Ixazomib or Lenalidomide combined with cyclophosphamide and dexamethasone in the treatment of elderly transplant-ineligible newly diagnosed multiple myeloma.Scientific reports · 2025Trial
- Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma.Cell reports. Medicine · 2024Trial
- 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
- Article
- A single-cell atlas of multiple myeloma defines malignant archetypes and proliferative states.Nature genetics · 2026Article
- Clinical Practice of Treatment Switch in Transplant-eligible Patients with Multiple Myeloma: An Exploratory Retrospective Analysis.Internal medicine (Tokyo, Japan) · 2026Article
- Comparison of gene fusion detection algorithms reveals frequently overlooked driver fusions in hematologic malignancies.NPJ precision oncology · 2026Article
- [Clinical characteristics and prognosis analysis of newly diagnosed multiple myeloma with t (4;14)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models.Blood cancer discovery · 2026Article
- An odyssey of monoclonal gammopathies: focusing on precursors and the progression from MGUS and SMM to multiple Myeloma, with a brief overview of novel therapeutic strategies.Clinical and experimental medicine · 2026Review
- Article
- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- Fulminant extramedullary relapse of multiple myeloma with rare cardiac, vascular, and multivisceral involvement: A case report.Therapeutic advances in hematology · 2026Article
- Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review.Blood and lymphatic cancer : targets and therapy · 2026Review
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- Human preclinical multiple myeloma in vitro models for disease modeling and therapy screening.Journal of biological engineering · 2025Review
- Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders.Leukemia · 2025Review
- [Prognostic value of high-risk cytogenetic abnormalities inmultiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Although translocation events between chromosome 4 (NSD2 gene) and chromosome 14 (immunoglobulin heavy chain [IgH] locus) (t(4;14)) is considered high risk in newly diagnosed multiple myeloma (NDMM), only ∼30% to 40% of t(4;14) patients are clinically high risk. We generated and compared a large whole genome sequencing (WGS) and transcriptome (RNA sequencing) from 258 t(4;14) (n = 153 discovery, n = 105 replication) and 183 non-t(4;14) NDMM patients with associated clinical data. A landmark survival analysis indicated only ∼25% of t(4;14) patients had an overall survival (OS) <24 months, and a comparative analysis of the patient subgroups identified biomarkers associated with this poor outcome, including translocation breakpoints located in the NSD2 gene and expression of IgH-NSD2 fusion transcripts. Three breakpoints were identified and are designated as: "no-disruption" (upstream of NSD2), "early-disruption" (in the 5' UTR), and "late-disruption" (within the NSD2 gene). Our results show a significant difference in OS based on the location of DNA breakpoints (median OS 28.6 "late-disruption" vs 59.2 "early disruption" vs 75.1 months "no disruption"). These findings have been replicated in an independent replication dataset. Also, univariate and multivariate analysis suggest high-risk markers such as del17p, 1p independently contribute to poor outcome in t(4;14) MM patients.
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