Trial reportBlood2014
Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy.
Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Clinical Significance of Circulating Cell-Free DNA Detection in Multiple Myeloma: A Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Liquid Biopsy as a Means of Assessing Prognosis and Identifying Novel Risk Factors in Multiple Myeloma.International journal of molecular sciences · 2025Article
- Impact of NRAS mutation on efficacy of triplet induction therapy in newly diagnosed multiple myeloma.Journal of clinical and experimental hematopathology : JCEH · 2025Article
- The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2024Review
- Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.HemaSphere · 2024Article
- Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology.Cancer pathogenesis and therapy · 2024Article
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities.International journal of molecular sciences · 2024Review
- The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.Pharmacogenomics and personalized medicine · 2024Review
- Article
- Molecular genetic aberrations in the pathogenesis of multiple myeloma.Asian biomedicine : research, reviews and news · 2023Review
- Plasma cell myeloma with RAS/BRAF mutations is frequently associated with a complex karyotype, advanced stage disease, and poorer prognosis.Cancer medicine · 2023Article
- Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again.Hematology reports · 2023Review
- HRAS mutation positive multiple myeloma in the type 2 CALR mutation positive essential thrombocythemia: A case report.Journal of cellular and molecular medicine · 2023Article
- The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma.Translational oncology · 2022Review
- Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model.Scientific reports · 2022Article
- Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma.Leukemia · 2022Article
- secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics.Blood cancer journal · 2022Article
- Pathogenic signaling in multiple myeloma.Seminars in oncology · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
Abstract
Various translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41 known oncogenes and tumor suppressor genes in tumor samples from 133 relapsed myeloma patients participating in phase 2 or 3 clinical trials of bortezomib. DNA mutations were identified in 14 genes. BRAF as well as RAS genes were mutated in a large proportion of cases (45.9%) and these mutations were mutually exclusive. New recurrent mutations were also identified, including in the PDGFRA and JAK3 genes. NRAS mutations were associated with a significantly lower response rate to single-agent bortezomib (7% vs 53% in patients with mutant vs wild-type NRAS, P = .00116, Bonferroni-corrected P = .016), as well as shorter time to progression in bortezomib-treated patients (P = .0058, Bonferroni-corrected P = .012). However, NRAS mutation did not impact outcome in patients treated with high-dose dexamethasone. KRAS mutation did not reduce sensitivity to bortezomib or dexamethasone. These findings identify a significant clinical impact of NRAS mutation in myeloma and demonstrate a clear example of functional differences between the KRAS and NRAS oncogenes.
Indexed as
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What OpenQuestion holds
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.