ArticleHaematologica2022
Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Pooled it
- 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
- Review
- Article
- The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance.Molecular diagnosis & therapy · 2026Review
- The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D.Leukemia · 2026Article
- Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.Discover oncology · 2026Review
- Genomic Insights into Tumorigenesis in Newly Diagnosed Multiple Myeloma.Diagnostics (Basel, Switzerland) · 2025Article
- Article
- Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond.Haematologica · 2025Review
- Investigating the role of tumor cell heterogeneity and angiogenesis genes in the prognosis of multiple myeloma.Frontiers in immunology · 2025Article
- Impact of NRAS mutation on efficacy of triplet induction therapy in newly diagnosed multiple myeloma.Journal of clinical and experimental hematopathology : JCEH · 2025Article
- Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.International journal of molecular sciences · 2024Article
- What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?Pflugers Archiv : European journal of physiology · 2024Review
- Recent Advances in The Definition of the Molecular Alterations Occurring in Multiple Myeloma.Mediterranean journal of hematology and infectious diseases · 2024Review
- Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival.Blood cancer journal · 2023Article
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- Tracking the evolution of therapy-related myeloid neoplasms using chemotherapy signatures.Blood · 2023Article
- Review
- Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma.Blood advances · 2023Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. In this study, we performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity; the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients; a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies.
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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.