Myeloma articles within Nature Communications

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  • Article
    | Open Access

    Chimeric antigen receptors (CAR) use antibody variable regions to activate anti-tumor immunity. Here the authors show that a mouse IgH/IgL variable region used in a clinical CAR induces host immune responses to possibly reduce therapy efficacy, but an IgH-only CAR T design achieves similar CAR T activity but is potentially less immunogenic.

    • Norris Lam
    • , Nathan D. Trinklein
    •  & James N. Kochenderfer

  • Article
    | Open Access

    In multiple myeloma, a 4;14 translocation induces overexpression of histone methyltransferase NSD2, resulting in expansion of H3K36me2 and shrinkage of H3K27me3 domains. Here the authors find that CTCF, H3K27ac and gene expression changes cluster within a subset of insulated domains implicating 3D chromosome organization as a key factor in the NSD2-mediated phenotype.

    • Priscillia Lhoumaud
    • , Sana Badri
    •  & Jane A. Skok

  • Article
    | Open Access

    Mutational signature analysis provides important information about the mutational processes underpinning different stages of tumorigenesis. Here, the authors compare publicly available signature extraction tools and suggest a framework for the generation of accurate and reproducible signature data.

    • Francesco Maura
    • , Andrea Degasperi
    •  & Niccolò Bolli

  • Article
    | Open Access

    Multiple myeloma is frequently characterised by translocation of genes next to the immunoglobulin heavy chain locus. In this study, the authors sequence a large cohort of high risk myeloma samples and find translocations of cMyc to the immunoglobulin heavy chain locus and this is associated with poor prognosis.

    • Benjamin G. Barwick
    • , Paola Neri
    •  & Lawrence H. Boise

  • Article
    | Open Access

    High expression of Mcl-1 promotes tumorigenesis and resistance to anticancer therapies. Here they report a macrocyclic molecule with high selectivity and affinity for Mcl-1 that exhibits potent anti-tumor effects as single agent and in combination with bortezomib or venetoclax in preclinical models of multiple myeloma and acute myeloid leukemia.

    • Adriana E. Tron
    • , Matthew A. Belmonte
    •  & Alexander W. Hird

  • Article
    | Open Access

    The mechanisms through which gut microbiota affect extramucosal tumors are poorly understood. Here the authors show that the gut microbiota promotes multiple myeloma by inducing differentiation and migration of Th17 cells in the bone marrow resulting also in increased recruitment of pro-tumorigenic eosinophils.

    • Arianna Calcinotto
    • , Arianna Brevi
    •  & Matteo Bellone

  • Article
    | Open Access

    Multiple myeloma is a cancer of the plasma cells, and the complete aetiology of the disease is still unclear. Here the authors perform an additional GWAS analysis followed by a meta-analysis with existing GWAS and replication genotyping and identify 6 novel risk loci and utilise gene expression, epigenetic profiling and in situ Hi-C data to further our understanding of MM susceptibility.

    • Molly Went
    • , Amit Sud
    •  & Stephen N. Thibodeau

  • Article
    | Open Access

    Smoldering MM (SMM) is a premalignant stage of multiple myeloma (MM). Here the authors perform whole genome sequencing of unique paired samples of SMM progressing to MM, and show that the genomic landscape at the SMM stage is very similar to MM, but trajectories of evolution can vary from patient to patient.

    • Niccolò Bolli
    • , Francesco Maura
    •  & Nikhil Munshi

  • Article
    | Open Access

    Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) enables characterization of a patient’s cancer. Here, the authors analyse CTCs, cfDNA, and tumor biopsies from multiple myeloma patients to show these approaches are complementary for mutation detection, together enabling a greater fraction of patient tumors to be profiled.

    • S. Manier
    • , J. Park
    •  & I. M. Ghobrial

  • Article
    | Open Access

    ELL2 was recently discovered as a susceptibility gene for multiple myeloma (MM). Here, they show that the MM risk allele lowers ELL2 expression in plasma cells, that it also upregulates gene sets related to ribosome biogenesis, and that one of the linked variants reduces binding of MAFF/G/K family transcription factors.

    • Mina Ali
    • , Ram Ajore
    •  & Björn Nilsson

  • Article
    | Open Access

    IKZF1 is a transcription factor known to regulate mammalian B-cell development. Here the authors show that IKZF1 is required for human pDC development and regulation of DC cytokine production in patients with IKZF1 haploinsufficiency, findings which are recapitulated in lenalidomide-induced IKZF1 deficiency.

    • Urszula Cytlak
    • , Anastasia Resteu
    •  & Venetia Bigley

  • Article
    | Open Access

    The treatment of multiple myeloma is challenging due to high relapse rates. Here the authors show that expression of ADAR1 correlates with poor patient outcomes, and that ADAR1-mediated editing of GLI1 is a mechanism relevant in the context of multiple myeloma progression and drug resistance.

    • Elisa Lazzari
    • , Phoebe K. Mondala
    •  & Catriona H. M. Jamieson

  • Article
    | Open Access

    Multiple myeloma is a malignancy of plasma cells in the blood. Here, the authors establish the landscape of fusion genes within this disease, identifying novel recurrent fusion genes that impact survival and may drive disease progression.

    • A. Cleynen
    • , R. Szalat
    •  & H. Avet-Loiseau

  • Article
    | Open Access

    FAM46C is one of the most frequently mutated genes in multiple myeloma (MM), but its molecular function remains unknown. Here the authors show that FAM46C is a poly(A) polymerase and that loss of function of FAM46C drives multiple myeloma through the destabilisation of ER response transcripts.

    • Seweryn Mroczek
    • , Justyna Chlebowska
    •  & Andrzej Dziembowski

  • Article
    | Open Access

    Genome wide association studies have identified multiple risk loci for multiple myeloma. Here, the authors show that the expression of CDCA7Lis associated with patient survival and expression of the gene is influenced by a risk variant at 7p15.3, which creates a transcription factor binding site for IRF4.

    • Ni Li
    • , David C. Johnson
    •  & Richard S. Houlston

  • Article
    | Open Access

    Previous genome-wide association studies have identified loci associated with the risk of multiple myeloma. Here, the authors present a meta-analysis of six genome wide association studies of the disease and identify eight new loci; functional studies identify genes as candidates for the basis of these associations.

    • Jonathan S. Mitchell
    • , Ni Li
    •  & Richard S. Houlston

  • Article
    | Open Access

    Several histone modifiers have been implicated in the survival of multiple myeloma cells. Here, the authors reveal a role for the histone demethylase KDM3A in the survival of this haematologic cancer, and show that mechanistically KDM3A removes H3K9 methylation from the promoters of KLF2 and IRF4, genes essential for myeloma cell survival.

    • Hiroto Ohguchi
    • , Teru Hideshima
    •  & Kenneth C. Anderson

  • Article |

    NF-κB has largely been known as a transcriptional activator. Here the authors show that a transcriptionally repressive NF-κB complex, HDAC4–RelB–p52, maintains repressive chromatin at proapoptotic genes Bim and BMF, and regulates multiple myeloma survival and growth in an ERK1 dependent manner.

    • Subrahmanya D. Vallabhapurapu
    • , Sunil K. Noothi
    •  & Sivakumar Vallabhapurapu

  • Article
    | Open Access

    Multiple myeloma is an incurable and fatal disease characterized by uninhibited growth of plasma cells in the bone marrow. Here, Swaminathan et al. conduct a genome-wide association study and identify a novel risk locus at ELL2, which encodes a key component of the super-elongation complex.

    • Bhairavi Swaminathan
    • , Guðmar Thorleifsson
    •  & Björn Nilsson

  • Article
    | Open Access

    Multiple myeloma is a malignant plasma cell disorder with a complex molecular pathogenesis. Here, the authors perform whole-exome sequencing, copy-number profiling and cytogenetic analysis in 84 myeloma samples and highlight the diversity and evolution of the mutational profile underlying the disease.

    • Niccolo Bolli
    • , Hervé Avet-Loiseau
    •  & Nikhil C. Munshi

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