ArticleJournal of hematology & oncology2018
Whole-exon sequencing of human myeloma cell lines shows mutations related to myeloma patients at relapse with major hits in the DNA regulation and repair pathways.
Article in Journal of hematology & oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Breaking the Balance: Baseline Oxidative Stress and DNA Repair Capacity in Multiple Myeloma Therapy.Cancers · 2026Article
- Association Between Polymorphisms in Genes Encoding PD-1/PD-L1 Molecules and Clinicopathological Features in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2026Article
- VS-4718 enhances apoptosis induced by low-dose carfilzomib and overcomes carfilzomib resistance in PSMB5-mutated proteasome inhibitor resistant multiple myeloma.Scientific reports · 2026Article
- Establishment and characterization of two patient-derived cell lines from a patient with gallbladder carcinoma.Translational cancer research · 2025Article
- Genetic and Epigenetic Aberrations ofCurrent issues in molecular biology · 2025Article
- Chromosome 1 Alterations in Multiple Myeloma: Considerations for Precision Therapy.European journal of haematology · 2025Review
- DNA damage repair-related methylated genes RRM2 and GAPDH are prognostic biomarkers associated with immunotherapy for lung adenocarcinoma.Genetics and molecular biology · 2025Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.HemaSphere · 2024Article
- MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes.Frontiers in immunology · 2024Review
- Multi-omics analysis of multiple myeloma patients with differential response to first-line treatment.Clinical and experimental medicine · 2023Article
- BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study.Frontiers in medicine · 2023Article
- The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM.Frontiers in neuroscience · 2023Review
- The epigenetic impact of suberohydroxamic acid and 5‑Aza‑2'‑deoxycytidine on DNMT3B expression in myeloma cell lines differing in IL‑6 expression.Molecular medicine reports · 2022Article
- Correlation of plasma cell assessment by phenotypic methods and molecular profiles by NGS in patients with plasma cell dyscrasias.BMC medical genomics · 2022Article
- Identification of clinical implications and potential prognostic models of chromatin regulator mutations in multiple myeloma.Clinical epigenetics · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- PD-L1Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman myeloma cell lines (HMCLs) are widely used for their representation of primary myeloma cells because they cover patient diversity, although not fully. Their genetic background is mostly undiscovered, and no comprehensive study has ever been conducted in order to reveal those details.
methodsWe performed whole-exon sequencing of 33 HMCLs, which were established over the last 50 years in 12 laboratories. Gene expression profiling and drug testing for the 33 HMCLs are also provided and correlated to exon-sequencing findings.
resultsMissense mutations were the most frequent hits in genes (92%). HMCLs harbored between 307 and 916 mutations per sample, with TP53 being the most mutated gene (67%). Recurrent bi-allelic losses were found in genes involved in cell cycle regulation (RB1, CDKN2C), the NFκB pathway (TRAF3, BIRC2), and the p53 pathway (TP53, CDKN2A). Frequency of mutations/deletions in HMCLs were either similar to that of patients (e.g., DIS3, PRDM1, KRAS) or highly increased (e.g., TP53, CDKN2C, NRAS, PRKD2). MAPK was the most altered pathway (82% of HMCLs), mainly by RAS mutants. Surprisingly, HMCLs displayed alterations in epigenetic (73%) and Fanconi anemia (54%) and few alterations in apoptotic machinery. We further identified mutually exclusive and associated mutations/deletions in genes involved in the MAPK and p53 pathways as well as in chromatin regulator/modifier genes. Finally, by combining the gene expression profile, gene mutation, gene deletion, and drug response, we demonstrated that several targeted drugs overcome or bypass some mutations.
conclusionsWith this work, we retrieved genomic alterations of HMCLs, highlighting that they display numerous and unprecedented abnormalities, especially in DNA regulation and repair pathways. Furthermore, we demonstrate that HMCLs are a reliable model for drug screening for refractory patients at diagnosis or at relapse.
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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.