Abstract:
:Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)-γ-related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ-dominant AML subtypes.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Vadakekolathu J,Minden MD,Hood T,Church SE,Reeder S,Altmann H,Sullivan AH,Viboch EJ,Patel T,Ibrahimova N,Warren SE,Arruda A,Liang Y,Smith TH,Foulds GA,Bailey MD,Gowen-MacDonald J,Muth J,Schmitz M,Cesano A,Pockleydoi
10.1126/scitranslmed.aaz0463subject
Has Abstractpub_date
2020-06-03 00:00:00issue
546eissn
1946-6234issn
1946-6242pii
12/546/eaaz0463journal_volume
12pub_type
杂志文章abstract::In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau1428
更新日期:2019-03-13 00:00:00
abstract::Physiologically relevant ALK (anaplastic lymphoma kinase) expression was not detected in human and mouse monocytes and macrophages, suggesting that the effects of bioactive compounds on stimulator of interferon genes (STING) activation may not depend on ALK. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.aar4321
更新日期:2018-12-12 00:00:00
abstract::Touch perception on the fingers and hand is essential for fine motor control, contributes to our sense of self, allows for effective communication, and aids in our fundamental perception of the world. Despite increasingly sophisticated mechatronics, prosthetic devices still do not directly convey sensation back to the...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008669
更新日期:2014-10-08 00:00:00
abstract::Hepatitis B virus (HBV)-induced hepatitis and carcinogen-induced hepatocellular carcinoma (HCC) are associated with serum androgen concentration. However, how androgen or the androgen receptor (AR) contributes to HBV-induced hepatocarcinogenesis remains unclear. We found that hepatic AR promotes HBV-induced hepatocarc...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001143
更新日期:2010-05-19 00:00:00
abstract::Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics, and viral pathogenesis concepts to simulate the activi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad6654
更新日期:2016-02-03 00:00:00
abstract::Paving the way for clinical trials, a new study shows that a glutamate receptor antagonist reduces repetitive behavior and social deficits in a mouse model of autism spectrum disorder. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3004017
更新日期:2012-04-25 00:00:00
abstract::Innate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines interleukin-5 (IL-5) and IL-13 and promot...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005374
更新日期:2013-01-30 00:00:00
abstract::Imaging, including its use for innovative tissue sampling, is slowly being recognized as playing a pivotal role in drug development, clinical trial design, and more effective delivery and monitoring of molecular therapies. The challenge is that, while a considerable number of new imaging technologies and new targeted ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aaf3936
更新日期:2016-09-07 00:00:00
abstract::Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested t...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aas9292
更新日期:2019-09-25 00:00:00
abstract::Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inherita...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002243
更新日期:2011-06-15 00:00:00
abstract::Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs in cardiac diseases is still limited. Global lncRNA expression profiling indicated that several lncRNA transcripts are deregulated during pressure overload-induced cardiac hypert...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf1475
更新日期:2016-02-17 00:00:00
abstract::Despite the remarkable enhancements in breast cancer classification and characterization, an exhaustive comprehension of the underlying carcinogenic processes and an accurate prediction of its clinical behavior are yet to be achieved. On the wave of recent scientific advances and clinical findings, new cutting-edge te...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001329
更新日期:2010-09-01 00:00:00
abstract::Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3000702
更新日期:2010-02-24 00:00:00
abstract::PTEN (phosphatase and tensin homolog) loss of function is the most common genetic aberration in endometrioid endometrial carcinomas. In addition to its well-described role in cell signaling, PTEN is involved in the maintenance of genomic stability. Loss of PTEN function causes defects in repair of DNA double-strand br...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001538
更新日期:2010-10-13 00:00:00
abstract::Emerging viral diseases pose ongoing health threats, particularly in an era of globalization; however, new biomedical research technologies such as genome sequencing and structure-based vaccine and drug design have improved our ability to respond to viral threats. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3009872
更新日期:2014-09-10 00:00:00
abstract::The clinical application of cytokine therapies for cancer treatment remains limited due to severe adverse reactions and insufficient therapeutic effects. Although cytokine localization by intratumoral administration could address both issues, the rapid escape of soluble cytokines from the tumor invariably subverts thi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaw2614
更新日期:2019-06-26 00:00:00
abstract::Osteoarthritis (OA) is a common degenerative condition that afflicts more than 70% of the population between 55 and 77 years of age. Although its prevalence is rising globally with aging of the population, current therapy is limited to symptomatic relief and, in severe cases, joint replacement surgery. We report that ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005409
更新日期:2013-03-13 00:00:00
abstract::Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat5857
更新日期:2019-06-12 00:00:00
abstract::Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat9223
更新日期:2019-02-27 00:00:00
abstract::Common variable immune deficiency (CVID) is the most common symptomatic primary immune deficiency, affecting ~1 in 25,000 persons. These patients suffer from impaired antibody responses, autoimmunity, and susceptibility to lymphoid cancers. To explore the cellular basis for these clinical phenotypes, we conducted high...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aab1216
更新日期:2015-08-26 00:00:00
abstract::Asthma is a clinically heterogeneous genetic disease, and its pathogenesis is incompletely understood. Genome-wide association studies link ORM (yeast)-Like protein isoform 3 [corrected] (ORMDL3), a member of the ORM gene family, to nonallergic childhood-onset asthma. Orm proteins negatively regulate sphingolipid (SL)...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005765
更新日期:2013-05-22 00:00:00
abstract::Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the smal...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.abc0441
更新日期:2020-08-26 00:00:00
abstract::As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aai8711
更新日期:2017-04-05 00:00:00
abstract::Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and progression. In contrast, only recently has attention been focused on the pathway that generates these regulatory molecules. The identification of neoplasia-associated germline mutations in DICER1 has focused translational research on compone...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3002493
更新日期:2011-11-30 00:00:00
abstract::Patients with rheumatoid arthritis (RA) may display atypical CD21-/lo B cells in their blood, but the implication of this observation remains unclear. We report here that the group of patients with RA and elevated frequencies of CD21-/lo B cells shows decreased ataxia telangiectasia-mutated (ATM) expression and activa...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaw4626
更新日期:2019-11-20 00:00:00
abstract::Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients more than 50 years of age. Previous therapeutic trials have targeted the inflammatory features of sIBM but all have failed. Because protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature o...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad4583
更新日期:2016-03-23 00:00:00
abstract::Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we foun...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3010525
更新日期:2015-02-25 00:00:00
abstract::Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aay1063
更新日期:2020-07-22 00:00:00
abstract::In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005972
更新日期:2013-10-23 00:00:00
abstract::Beginning with the 18th-century physician-scientist William Heberden, the elder, Science Translational Medicine introduces a new article series about historical figures whose transformational contributions to science, medicine, and society remain relevant today. ...
journal_title:Science translational medicine
pub_type: 历史文章,杂志文章
doi:10.1126/scitranslmed.aaa2250
更新日期:2015-05-13 00:00:00