Abstract:
:Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003-2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Mouhieddine TH,Sperling AS,Redd R,Park J,Leventhal M,Gibson CJ,Manier S,Nassar AH,Capelletti M,Huynh D,Bustoros M,Sklavenitis-Pistofidis R,Tahri S,Hornburg K,Dumke H,Itani MM,Boehner CJ,Liu CJ,AlDubayan SH,Reardon Bdoi
10.1038/s41467-020-16805-5subject
Has Abstractpub_date
2020-06-12 00:00:00pages
2996issue
1issn
2041-1723pii
10.1038/s41467-020-16805-5journal_volume
11pub_type
杂志文章abstract::Insulin-like growth factors (IGFs) induce proliferation of various cell types and play important roles in somatic growth and cancer development. Phosphorylation of insulin receptor substrate (IRS)-1/2 by IGF-I receptor tyrosine kinase is essential for IGF action. Here we identify Nedd4 as an IRS-2 ubiquitin ligase. Ne...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7780
更新日期:2015-04-16 00:00:00
abstract::The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRI...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms14004
更新日期:2017-01-13 00:00:00
abstract::Homologous recombination-mediated gene targeting has greatly contributed to genetic analysis in a wide range of species, but is highly inefficient in human cells because of overwhelmingly frequent random integration events, whose molecular mechanism remains elusive. Here we show that DNA polymerase θ, despite its mino...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms16112
更新日期:2017-07-11 00:00:00
abstract::Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene c...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16718-3
更新日期:2020-06-11 00:00:00
abstract::Bacterial contamination of biological channels, catheters or water resources is a major threat to public health, which can be amplified by the ability of bacteria to swim upstream. The mechanisms of this 'rheotaxis', the reorientation with respect to flow gradients, are still poorly understood. Here, we follow individ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11360-0
更新日期:2019-07-31 00:00:00
abstract::Mitochondria and peroxisomes proliferate by division. During division, a part of their membrane is pinched off by constriction of the ring-shaped mitochondrial division (MD) and peroxisome-dividing (POD) machinery. This constriction is mediated by a dynamin-like GTPase Dnm1 that requires a large amount of GTP as an en...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07009-z
更新日期:2018-11-06 00:00:00
abstract::Rabies virus (RABV) causes fatal encephalitis in more than 59,000 people yearly. Upon the bite of an infected animal, the development of clinical disease can be prevented with post-exposure prophylaxis (PEP), which includes the administration of Rabies immunoglobulin (RIG). However, the high cost and limited availabil...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14398-7
更新日期:2020-01-30 00:00:00
abstract::Ca2+ coordinates diverse cellular processes, yet how function-specific signals arise is enigmatic. We describe a cell-wide network of distinct cytoplasmic nanocourses with the nucleus at its centre, demarcated by sarcoplasmic reticulum (SR) junctions (≤400 nm across) that restrict Ca2+ diffusion and by nanocourse-spec...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10055-w
更新日期:2019-05-24 00:00:00
abstract::The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibr...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05220-6
更新日期:2018-07-24 00:00:00
abstract::RNA-binding proteins (RBPs) integrate the processing of RNAs into post-transcriptional gene regulation, but the direct contribution of them to myeloid cell specification is poorly understood. Here, we report the first global RBP transcriptomic analysis of myeloid differentiation by combining RNA-seq analysis with myel...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01425-3
更新日期:2017-11-10 00:00:00
abstract::The space charge layer (SCL) is generally considered one of the origins of the sluggish interfacial lithium-ion transport in all-solid-state lithium-ion batteries (ASSLIBs). However, in-situ visualization of the SCL effect on the interfacial lithium-ion transport in sulfide-based ASSLIBs is still a great challenge. He...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19726-5
更新日期:2020-11-18 00:00:00
abstract::Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellular conditions such a...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03984-5
更新日期:2018-05-14 00:00:00
abstract::Assessing the physical connections and allosteric communications in multi-domain nuclear receptor (NR) polypeptides has remained challenging, with few crystal structures available to show their overall structural organizations. Here we report the quaternary architecture of multi-domain retinoic acid receptor β-retinoi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00981-y
更新日期:2017-10-11 00:00:00
abstract::The large interest in chiral magnetic structures for realization of nanoscale magnetic storage or logic devices has necessitated methods which can quantify magnetic interactions at the atomic scale. To overcome the limitations of the typically used current-based sensing of atomic-scale exchange interactions, a force-b...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15024-2
更新日期:2020-03-05 00:00:00
abstract::In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While lo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16971-6
更新日期:2020-06-23 00:00:00
abstract::In mammals, a subset of arginine tRNA isoacceptors are methylated in the anticodon loop by the METTL2 methyltransferase to form the 3-methylcytosine (m3C) modification. However, the mechanism by which METTL2 identifies specific tRNA arginine species for m3C formation as well as the biological role of m3C in mammals is...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16321-6
更新日期:2020-05-19 00:00:00
abstract::NHE9 (SLC9A9) is an endosomal cation/proton antiporter with orthologues in yeast and bacteria. Rare, missense substitutions in NHE9 are genetically linked with autism but have not been functionally evaluated. Here we use evolutionary conservation analysis to build a model structure of NHE9 based on the crystal structu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3510
更新日期:2013-01-01 00:00:00
abstract::The efficiencies of perovskite solar cells (PSCs) are now reaching such consistently high levels that scalable manufacturing at low cost is becoming critical. However, this remains challenging due to the expensive hole-transporting materials usually employed, and difficulties associated with the scalable deposition of...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04028-8
更新日期:2018-04-24 00:00:00
abstract::The dynamic incorporation of histone variants influences chromatin structure and many biological processes. In Arabidopsis, the canonical variant H3.1 differs from H3.3 in four residues, one of which (H3.1Phe41) is unique and conserved in plants. However, its evolutionary significance remains unclear. Here, we show th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-02976-9
更新日期:2018-02-12 00:00:00
abstract::Direct reciprocity is a mechanism for cooperation among humans. Many of our daily interactions are repeated. We interact repeatedly with our family, friends, colleagues, members of the local and even global community. In the theory of repeated games, it is a tacit assumption that the various games that a person plays ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02721-8
更新日期:2018-02-07 00:00:00
abstract::The striking diversity of bird beak shapes is an outcome of natural selection, yet the relative importance of the limitations imposed by the process of beak development on generating such variation is unclear. Untangling these factors requires mapping developmental mechanisms over a phylogeny far exceeding model syste...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4700
更新日期:2014-04-16 00:00:00
abstract::Upon muscle injury, the high mobility group box 1 (HMGB1) protein is upregulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational leve...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3388
更新日期:2013-01-01 00:00:00
abstract::Gas-sensing materials are becoming increasingly important in our society, requiring high sensitivity to differentiate similar gases like N2 and O2. For the design of such materials, the driving force of electronic host-guest interaction or host-framework changes during the sorption process has commonly been considered...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07889-1
更新日期:2018-12-21 00:00:00
abstract::The host-guest recognition between two macrocycles to form hierarchical non-intertwined ring-in-ring assemblies remains an interesting and challenging target in noncovalent synthesis. Herein, we report the design and characterization of a box-in-box assembly on the basis of host-guest radical-pairing interactions betw...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07673-1
更新日期:2018-12-10 00:00:00
abstract::Spin-based devices offer non-volatile, scalable, low power and reprogrammable functionality for emerging device technologies. Here we fabricate nanoscale spintronic devices with ferromagnetic metal/single-layer graphene tunnel barriers used to generate spin accumulation and spin currents in a silicon nanowire transpor...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8541
更新日期:2015-06-19 00:00:00
abstract::Batesian mimicry, in which harmless species (mimics) deter predators by deceitfully imitating the warning signals of noxious species (models), generates striking cases of phenotypic convergence that are classic examples of evolution by natural selection. However, mimicry of venomous coral snakes has remained controver...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11484
更新日期:2016-05-05 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature communications
pub_type: 已发布勘误
doi:10.1038/s41467-020-14820-0
更新日期:2020-02-21 00:00:00
abstract::SIRT1, the founding member of the mammalian family of seven NAD(+)-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural eleme...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8645
更新日期:2015-07-02 00:00:00
abstract::The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system....
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2388
更新日期:2013-01-01 00:00:00
abstract::Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to antigen. Here we show that the heritable downregulation of CD8 during type 2 polarization of murine CD8(+) effector T cells in vitro and in vivo is associated with CpG methylation of several regions of the Cd8a locus. These epigenetic modi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4547
更新日期:2014-03-28 00:00:00