Abstract:
:Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered in AML genomes, we performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using 1.85 million feature SNP arrays. Acquired copy number alterations (CNAs) were confirmed using an ultra-dense array comparative genomic hybridization platform. A total of 201 somatic CNAs were found in the 86 AML genomes (mean, 2.34 CNAs per genome), with French-American-British system M6 and M7 genomes containing the most changes (10-29 CNAs per genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, whereas 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several CNA regions were recurrent. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes; 6 of 8 UPD calls occurred in samples with a normal karyotype. Collectively, 34 of 86 AML genomes (40%) contained alterations not found with cytogenetics, and 98% of these regions contained genes. Of 86 genomes, 43 (50%) had no CNA or UPD at this level of resolution. In this study of 86 adult AML genomes, the use of an unbiased high-resolution genomic screen identified many genes not previously implicated in AML that may be relevant for pathogenesis, along with many known oncogenes and tumor suppressor genes.
journal_name
Proc Natl Acad Sci U S Aauthors
Walter MJ,Payton JE,Ries RE,Shannon WD,Deshmukh H,Zhao Y,Baty J,Heath S,Westervelt P,Watson MA,Tomasson MH,Nagarajan R,O'Gara BP,Bloomfield CD,Mrózek K,Selzer RR,Richmond TA,Kitzman J,Geoghegan J,Eis PS,Maupin R,doi
10.1073/pnas.0903091106subject
Has Abstractpub_date
2009-08-04 00:00:00pages
12950-5issue
31eissn
0027-8424issn
1091-6490pii
0903091106journal_volume
106pub_type
杂志文章abstract::cDNA libraries were constructed from pathogenic (HM-1:IMSS) and nonpathogenic (SAW 1734) isolates of Entamoeba histolytica. A cDNA clone (cEH-P1) specific for pathogenic amoebae was identified by screening with a pool of sera from patients with invasive amoebiasis that had been absorbed with nonpathogenic amoebae. Thi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.13.5118
更新日期:1989-07-01 00:00:00
abstract::WE REEXAMINED TWO QUESTIONS CONCERNING LYT ANTIGENS OF CYTOTOXIC T CELLS OF THE MOUSE: is Lyt-1 antigen expressed on cytotoxic effector cells and can cytotoxicity be blocked by antibody to Lyt antigens in the absence of added complement? A 3-hr (51)Cr-release assay with splenic effector cells and leukemia or myeloma t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.4.1977
更新日期:1979-04-01 00:00:00
abstract::The influential role of Wnt5a in tumor progression underscores the requirement for developing molecules that can target Wnt5a-mediated cellular responses. In the aggressive skin cancer, melanoma, elevated Wnt5a expression promotes cell motility and drives metastasis. Two approaches can be used to counteract these effe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0909409106
更新日期:2009-11-17 00:00:00
abstract::Estrogen receptor beta (ER-beta) regulates diverse physiological functions in the human body. Current studies are confined to ER-beta1, and the functional roles of isoforms 2, 4, and 5 remain unclear. Full-length ER-beta4 and -beta5 isoforms were obtained from a prostate cell line, and they exhibit differential expres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0605676103
更新日期:2006-08-29 00:00:00
abstract::BSC-1 cells, epithelial cells of African green monkey kidney origin, show pronounced density-dependent regulation of growth in cell culture. Growth of the cells is rapid to a density of approximately 1.5 x 10(5) cells/per cm(2) in Dulbecco-modified Eagle's medium supplemented with 10% calf serum. Above this "saturatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.1.339
更新日期:1978-01-01 00:00:00
abstract::The oxazolidinones represent the first new class of antibiotics to enter into clinical usage within the past 30 years, but their binding site and mechanism of action has not been fully characterized. We have determined the crystal structure of the oxazolidinone linezolid bound to the Deinococcus radiodurans 50S riboso...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804276105
更新日期:2008-09-09 00:00:00
abstract::To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1404386111
更新日期:2014-10-28 00:00:00
abstract::An explosion of new information linking activation of cell surface signal initiators to changes in gene expression has recently emerged. The focus of much of this information has centered around the agonist-dependent activation of the mitogen-activated protein (MAP) kinases. Although this intracellular signal transduc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.90.13.5889
更新日期:1993-07-01 00:00:00
abstract::We carried out a large-scale screen to identify interactions between integral membrane proteins of Saccharomyces cerevisiae by using a modified split-ubiquitin technique. Among 705 proteins annotated as integral membrane, we identified 1,985 putative interactions involving 536 proteins. To ascribe confidence levels to...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0505482102
更新日期:2005-08-23 00:00:00
abstract::Three protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) were detected when the soluble fraction of rabbit kidney medulla was chromatographed on DEAE-cellulose with a linear NaC1 gradient. The first two kinases eluted (Peak 1 and Peak II) were cyclic-AMP-dependent, wheras Peak III was cyclic-AMP-independent...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.6.2197
更新日期:1975-06-01 00:00:00
abstract::Phylogenetic analysis of Plasmodium parasites has indicated that their modern-day distribution is a result of a series of human-mediated dispersals involving transport between Africa, Europe, America, and Asia. A major outstanding question is the phylogenetic affinity of the malaria causing parasites Plasmodium vivax ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1611017113
更新日期:2016-10-11 00:00:00
abstract::The DNA sequences of wheat Acc-1 and Acc-2 loci, encoding the plastid and cytosolic forms of the enzyme acetyl-CoA carboxylase, were analyzed with a view to understanding the evolution of these genes and the origin of the three genomes in modern hexaploid wheat. Acc-1 and Acc-2 loci from each of the wheats Triticum ur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803981105
更新日期:2008-07-15 00:00:00
abstract::Netrin-1 is critical for axonal pathfinding which shares similarities with formation of vascular network. Here we report that netrin-1 induction of angiogenesis is mediated by an increase in endothelial nitric oxide (NO*) production, which occurs via a DCC-dependent, ERK1/2-eNOS feed-forward mechanism. Exposure of mat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0511011103
更新日期:2006-04-25 00:00:00
abstract::Efficient apoptotic cell clearance and induction of immunologic tolerance is a critical mechanism preventing autoimmunity and associated pathology. Our laboratory has reported that apoptotic cells induce tolerance by a mechanism dependent on the tryptophan catabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) in sp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1504276112
更新日期:2015-08-25 00:00:00
abstract::Social status motivates much of human behavior. However, status may have been a relatively weak target of selection for much of human evolution if ancestral foragers tended to be more egalitarian. We test the "egalitarianism hypothesis" that status has a significantly smaller effect on reproductive success (RS) in for...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1606800113
更新日期:2016-09-27 00:00:00
abstract::Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1008950108
更新日期:2011-01-04 00:00:00
abstract::Plants have evolved adaptive strategies that involve transcriptional networks to cope with and survive environmental challenges. Key transcriptional regulators that mediate responses to environmental fluctuations in nitrate have been identified; however, little is known about how these regulators interact to orchestra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1615676114
更新日期:2017-02-28 00:00:00
abstract::The development of distinct regions in the amniote vertebral column results from somite formation and Hox gene expression, with the adult morphology displaying remarkable variation among lineages. Mammalian regionalization is reportedly very conservative or even constrained, but there has been no study investigating v...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0912622107
更新日期:2010-02-02 00:00:00
abstract::We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1118833109
更新日期:2012-01-31 00:00:00
abstract::Freezing avoidance conferred by different types of antifreeze proteins in various polar and subpolar fishes represents a remarkable example of cold adaptation, but how these unique proteins arose is unknown. We have found that the antifreeze glycoproteins (AFGPs) of the predominant Antarctic fish taxon, the notothenio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.8.3811
更新日期:1997-04-15 00:00:00
abstract::Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM+ IgD+ B cells in vivo to address the fate of lymp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.22.13171
更新日期:1998-10-27 00:00:00
abstract::The regulatory photoreceptor phytochrome controls the transcription of its own phy genes in a negative feedback fashion. We have exploited microprojectile-mediated gene transfer to develop a rapid transient expression assay system for the study of DNA sequences involved in the phytochrome-regulated expression of these...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.24.9692
更新日期:1989-12-01 00:00:00
abstract::Indirect immunofluorescent analysis revealed that sera from five patients with subacute sclerosing panencephalitis possessed IgD antibodies directed against measles virus components in persistently infected HeLa cells. IgD levels in these sera were within the normal range. Control studies indicated that the reaction w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.4.1297
更新日期:1976-04-01 00:00:00
abstract::Nitrofurans, a class of antibacterial drugs in extensive use, interferes with gene expression in a highly specific manner. While in the low dose range (0.5-25 mug/ml), 5-nitro-2-furfurylidene-1-aminohydantoin has no effect on transcription, it inhibits specifically the expression of one class of genes in translation. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.10.3386
更新日期:1976-10-01 00:00:00
abstract::Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian syste...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1516953113
更新日期:2016-03-08 00:00:00
abstract::We describe the effect of a 200-microns wavelength free electron laser beam on the ability of asynchronized and synchronized mammalian tissue culture cells to incorporate tritiated thymidine. Compared to controls (unexposed cells), a significant proportion of exposed cells exhibited a reduction in isotope incorporatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.7.2810
更新日期:1990-04-01 00:00:00
abstract::Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1213364110
更新日期:2013-02-12 00:00:00
abstract::The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.21.11614
更新日期:2000-10-10 00:00:00
abstract::Conditional mutations such as temperature-sensitive (ts) mutations are important for the analysis of protein function but are often difficult, or impossible, to obtain. Here we present a simple method for generating conditional mutations based on the use of a protein-destabilizing genetic element in combination with s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.4.1249
更新日期:1992-02-15 00:00:00
abstract::Social networks exhibit strikingly systematic patterns across a wide range of human contexts. Although genetic variation accounts for a significant portion of the variation in many complex social behaviors, the heritability of egocentric social network attributes is unknown. Here, we show that 3 of these attributes (i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0806746106
更新日期:2009-02-10 00:00:00