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1.
Circ Cardiovasc Imaging ; 14(12): 1133-1146, 2021 12.
Article in English | MEDLINE | ID: mdl-34915726

ABSTRACT

The risk of coronary heart disease (CHD) clinical manifestations and patient management is estimated according to risk scores accounting multifactorial risk factors, thus failing to cover the individual cardiovascular risk. Technological improvements in the field of medical imaging, in particular, in cardiac computed tomography angiography and cardiac magnetic resonance protocols, laid the development of radiogenomics. Radiogenomics aims to integrate a huge number of imaging features and molecular profiles to identify optimal radiomic/biomarker signatures. In addition, supervised and unsupervised artificial intelligence algorithms have the potential to combine different layers of data (imaging parameters and features, clinical variables and biomarkers) and elaborate complex and specific CHD risk models allowing more accurate diagnosis and reliable prognosis prediction. Literature from the past 5 years was systematically collected from PubMed and Scopus databases, and 60 studies were selected. We speculated the applicability of radiogenomics and artificial intelligence through the application of machine learning algorithms to identify CHD and characterize atherosclerotic lesions and myocardial abnormalities. Radiomic features extracted by cardiac computed tomography angiography and cardiac magnetic resonance showed good diagnostic accuracy for the identification of coronary plaques and myocardium structure; on the other hand, few studies exploited radiogenomics integration, thus suggesting further research efforts in this field. Cardiac computed tomography angiography resulted the most used noninvasive imaging modality for artificial intelligence applications. Several studies provided high performance for CHD diagnosis, classification, and prognostic assessment even though several efforts are still needed to validate and standardize algorithms for CHD patient routine according to good medical practice.


Subject(s)
Artificial Intelligence , Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Imaging Genomics/methods , Magnetic Resonance Imaging/methods , Coronary Vessels/diagnostic imaging , Humans , Precision Medicine/methods
2.
FEBS J ; 288(21): 6087-6094, 2021 11.
Article in English | MEDLINE | ID: mdl-34719878

ABSTRACT

Anthony Letai is Professor in Medicine at Harvard Medical School and Dana Farber Cancer Institute, and President of The Society for Functional Precision Medicine. Among Tony's scientific achievements, work from his lab contributed toward the FDA approval of Venetoclax combination treatment for adult acute myeloid leukemia (AML) patients. Moreover, his studies on cancer cell death have led to the development of BH3 profiling, an assay that allows for the definition of how close a cell is to the threshold required to commit to apoptosis, which can be used to improve clinical outcomes for cancer patients. In this interview, Tony relays the story behind some of his scientific breakthroughs, discusses the importance of function when designing targeted cancer therapies, gives an overview of BH3 profiling and its application to cancer therapy, and recalls the key events and collaborations that drove his successful research career.


Subject(s)
Precision Medicine/methods , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Humans , Leukemia, Myeloid, Acute/drug therapy , Sulfonamides/therapeutic use
3.
Int J Mol Sci ; 22(19)2021 Oct 03.
Article in English | MEDLINE | ID: mdl-34639060

ABSTRACT

Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain is a cancer hallmark that leads to recurrence despite surgical resection. With the emergence of precision medicine, patient-derived 3D systems are considered potentially robust GBM preclinical models. In this study, we screened a library of 22 anti-invasive compounds (i.e., NF-kB, GSK-3-B, COX-2, and tubulin inhibitors) using glioblastoma U-251 MG cell spheroids. We evaluated toxicity and invasion inhibition using a 3D Matrigel invasion assay. We next selected three compounds that inhibited invasion and screened them in patient-derived glioblastoma organoids (GBOs). We developed a platform using available macros for FIJI/ImageJ to quantify invasion from the outer margin of organoids. Our data demonstrated that a high-throughput invasion screening can be done using both an established cell line and patient-derived 3D model systems. Tubulin inhibitor compounds had the best efficacy with U-251 MG cells, however, in ex vivo patient organoids the results were highly variable. Our results indicate that the efficacy of compounds is highly related to patient intra and inter-tumor heterogeneity. These results indicate that such models can be used to evaluate personal oncology therapeutic strategies.


Subject(s)
Biological Specimen Banks , Brain Neoplasms/pathology , Drug Discovery , Glioblastoma/pathology , Organoids , Precision Medicine , Antineoplastic Agents/pharmacology , Brain Neoplasms/drug therapy , Cell Line, Tumor , Drug Discovery/methods , Drug Screening Assays, Antitumor/methods , Glioblastoma/drug therapy , Humans , Neoplasm Invasiveness , Precision Medicine/methods , Spheroids, Cellular , Tissue Culture Techniques
6.
Nat Commun ; 12(1): 6260, 2021 10 29.
Article in English | MEDLINE | ID: mdl-34716306

ABSTRACT

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants.


Subject(s)
Biomimetic Materials , Cochlea/physiopathology , Cochlear Implants , Machine Learning , Printing, Three-Dimensional , Cochlea/diagnostic imaging , Cochlear Implantation , Dielectric Spectroscopy , Humans , Neural Networks, Computer , Precision Medicine/methods , Reproducibility of Results , X-Ray Microtomography
7.
Am J Respir Crit Care Med ; 204(8): 891-901, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34652268

ABSTRACT

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non-critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4) further development of the tools necessary for the real-time application of precision medicine approaches; 5) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.


Subject(s)
Biomedical Research/methods , Critical Care/methods , Observational Studies as Topic/methods , Precision Medicine/methods , Randomized Controlled Trials as Topic/methods , Respiratory Distress Syndrome/therapy , Sepsis/therapy , Humans
8.
Nat Commun ; 12(1): 5348, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34504071

ABSTRACT

Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores-fully electronic sensors with single-molecule sensitivity-are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence ("1") or absence ("0") of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format.


Subject(s)
Biomarkers/blood , Immunoassay/methods , Nanopores , Nanotechnology/methods , Thyrotropin/blood , Algorithms , Blood Proteins/analysis , DNA/chemistry , Humans , Precision Medicine/methods , Reproducibility of Results , Sensitivity and Specificity
9.
Cancer Sci ; 112(11): 4425-4432, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34510657

ABSTRACT

Comprehensive genomic profiling enables the detection of genomic biomarkers in advanced solid tumors. However, efficient patient screening for the success of precision oncology remains challenging due to substantial barriers, such as genotyping costs and accessibility to matched therapies. To address these challenges, we launched GI-SCREEN, a nationwide gastrointestinal cancer genomic screening project within the SCRUM-Japan network in 2015 with the specific purpose of matching patients with a diverse portfolio of affiliated interventional targeted therapy trials. Subsequently, we initiated the molecular profiling projects GOZILA, MONSTAR-SCREEN-1, and MONSTAR-SCREEN-2, which incorporate tissue and plasma multiomics approaches to accurately identify patients with advanced solid tumors who would benefit from matched therapies. These projects have led to a significant increase in patient participation in targeted clinical trials and the approval of several therapeutics and companion diagnostics. Additionally, clinicogenomic analyses utilizing the SCRUM-Japan database have provided new insights into the molecular mechanisms of advanced solid tumors. In this review, we describe the path to the realization of cancer precision medicine for patients with advanced solid tumors based on the SCRUM-Japan GI-SCREEN and MONSTAR-SCREEN platforms.


Subject(s)
Circulating Tumor DNA/genetics , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/therapy , Medical Oncology/methods , Precision Medicine/methods , Databases, Genetic , Gastrointestinal Neoplasms/pathology , Gene Expression Profiling/methods , Genetic Markers , High-Throughput Nucleotide Sequencing , Humans , Japan , Registries
10.
Int J Mol Sci ; 22(18)2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34575825

ABSTRACT

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.


Subject(s)
Aptamers, Nucleotide , COVID-19 , Precision Medicine/methods , SELEX Aptamer Technique/methods , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , Humans
11.
Int J Mol Sci ; 22(18)2021 Sep 08.
Article in English | MEDLINE | ID: mdl-34575878

ABSTRACT

Glutamate, a crucial excitatory neurotransmitter, plays a major role in the modulation of schizophrenia's pathogenesis. New drug developments for schizophrenia have been prompted by the hypoglutamatergic hypothesis of schizophrenia. The cystine/glutamate antiporter system xc- is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of xc- subunits-the solute carrier (SLC) family 3 member 2 and the SLC family 7 member 11. We searched for relevant studies from 1980, when Bannai and Kitamura first identified the protein subunit system xc- in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter xc-, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal xc-, causing glutamate efflux. Next, excitatory amino acid transporters enhance the unidirectional transportation of glutamate and sodium. These two biochemical pathways are also crucial to the production of glutathione, a protective agent for neural and glial cells and astrocytes. Investigation of the expression of system xc- genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia. In addition, the findings further support the hypoglutamatergic hypothesis of schizophrenia.


Subject(s)
Antiporters/genetics , Antiporters/metabolism , Cystine/metabolism , Disease Susceptibility , Glutamic Acid/metabolism , Schizophrenia/etiology , Schizophrenia/metabolism , Animals , Biological Transport , Biomarkers , Disease Management , Humans , Neurons/metabolism , Neurotransmitter Agents/metabolism , Oxidative Stress/drug effects , Precision Medicine/methods , Schizophrenia/diagnosis , Schizophrenia/therapy , Synaptic Transmission
12.
Int J Mol Sci ; 22(18)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34576266

ABSTRACT

Targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia remains a significant unmet need. Recently, new drugs have attempted to improve the outcomes of this poor molecular subgroup. The aim of this article is to review all the current knowledge using active agents including hypomethylating agents with venetoclax, eprenetapopt or magrolimab. We include comprehensive analysis of clinical trials to date evaluating these drugs in TP53 myeloid neoplasms as well as discuss future novel combinations for consideration. Additionally, further understanding of the unique clinicopathologic components of TP53 mutant myeloid neoplasms versus wild-type is critical to guide future study. Importantly, the clinical trajectory of patients is uniquely tied with the clonal burden of TP53, which enables serial TP53 variant allele frequency analysis to be a critical early biomarker in investigational studies. Together, significant optimism is now possible for improving outcomes in this patient population.


Subject(s)
Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Mutation , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Precision Medicine/methods , Tumor Suppressor Protein p53/genetics , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents/administration & dosage , Biomarkers/metabolism , Biomarkers, Tumor , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Clinical Trials as Topic , Humans , Quinuclidines/administration & dosage , Sulfonamides/administration & dosage , Treatment Outcome , Tumor Suppressor Protein p53/metabolism
13.
Nutrients ; 13(9)2021 Aug 25.
Article in English | MEDLINE | ID: mdl-34578835

ABSTRACT

The body composition of patients with celiac disease (CD), on which the effects of a gluten-free diet (GFD) are controversial, differs from that of the average population. In this study, we aimed to compare the body composition across CD patients before a GFD, CD patients after a one-year GFD and non-celiac control subjects. A systematic search was conducted using five electronic databases up to 15 July 2021 for studies that reported at least one of the pre-specified outcomes. In meta-analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. A total of 25 studies were eligible for systematic review, seven of which were included in meta-analysis. During a ≥1-year GFD, fat mass of CD patients, compared to that at baseline, significantly increased (WMD = 4.1 kg, 95% CI = 1.5 to 6.6, three studies). In CD patients after a ≥1-year GFD, compared to non-celiac controls, fat mass (WMD = -5.8 kg, 95% CI = -8.7 to -2.9, three studies) and fat-free mass (WMD = -1.9 kg, 95% CI = -3.0 to -0.7, three studies) were significantly lower. In conclusion, body composition-related parameters of CD patients differ from that of the non-celiac control subjects even after a longstanding GFD.


Subject(s)
Adipose Tissue , Body Composition , Celiac Disease/diet therapy , Counseling/methods , Diet, Gluten-Free/methods , Databases, Factual , Humans , Precision Medicine/methods
14.
Br J Radiol ; 94(1127): 20210576, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34520242

ABSTRACT

FDG-PET scanning has a central role in lymphoma staging and response assessment. There is a growing body of evidence that PET response assessment during and after initial systemic therapy can provide useful prognostic information, and PET response has an evolving role in guiding patient care. This review provides a perspective on the role of PET response assessment for individualised management of patients with the most common aggressive lymphomas, Hodgkin lymphoma and diffuse large B-cell lymphoma.


Subject(s)
Hodgkin Disease/diagnostic imaging , Hodgkin Disease/therapy , Lymphoma, Non-Hodgkin/diagnostic imaging , Lymphoma, Non-Hodgkin/therapy , Positron-Emission Tomography/methods , Precision Medicine/methods , Humans , Lymph Nodes/diagnostic imaging
15.
Br J Radiol ; 94(1127): 20210609, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34520671

ABSTRACT

The use of 18F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.(1, 2) The utility of PET as a predictive imaging biomarker in assessing treatment success or failure has been investigated extensively in malignant lymphomas. Considerable progress has been made over the last decade, in using PET to direct more personalised "risk-adapted" approaches, as well as an increased understanding of some of the limitations. Arguably the greatest success has been in Hodgkin Lymphoma (HL) where PET was initially demonstrated to be a powerful predictive biomarker (3) and is now routinely used in both early-stage and advanced HL to reduce or escalate the use of chemotherapy as well as guiding the delivery of more selective radiotherapy to patients.


Subject(s)
Lymphoma/diagnostic imaging , Lymphoma/therapy , Positron-Emission Tomography/methods , Precision Medicine/methods , Radiography, Interventional/methods , Humans , Positron Emission Tomography Computed Tomography/methods , Treatment Outcome
16.
Crit Care ; 25(1): 330, 2021 09 10.
Article in English | MEDLINE | ID: mdl-34507597

ABSTRACT

There is ongoing demographic ageing and increasing longevity of the population, with previously devastating and often-fatal diseases now transformed into chronic conditions. This is turning multi-morbidity into a major challenge in the world of critical care. After many years of research and innovation, mainly in geriatric care, the concept of multi-morbidity now requires fine-tuning to support decision-making for patients along their whole trajectory in healthcare, including in the intensive care unit (ICU). This article will discuss current challenges and present approaches to adapt critical care services to the needs of these patients.


Subject(s)
Multimorbidity/trends , Precision Medicine/methods , Aged , Aged, 80 and over , Critical Care/methods , Critical Care/trends , Female , Humans , Male , Precision Medicine/trends , Prognosis , Risk Assessment/methods
17.
Neurology ; 97(17): 817-831, 2021 10 26.
Article in English | MEDLINE | ID: mdl-34493617

ABSTRACT

A monogenic etiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities, and treatment choices. In this narrative review, we summarize concepts on the genetic epilepsies based on the underlying pathophysiologic mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. Most monogenic disorders are very rare and ASM choices for them are still based on inferences drawn from observational studies and early, often anecdotal, experiences with precision therapies. Precision medicine remains applicable to only a narrow number of patients with monogenic epilepsies and may target only part of the actual functional defects. Phenotypic heterogeneity is remarkable, and some genetic mutations activate epileptogenesis through their developmental effects, which may not be reversed postnatally. Other genes seem to have pure functional consequences on excitability, acting through either loss- or gain-of-function effects, and these may have opposite treatment implications. In addition, the functional consequences of missense mutations may be difficult to predict, making precision treatment approaches considerably more complex than estimated by deterministic interpretations. Knowledge of genetic etiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification, and functional characterization of specific somatic mutations before surgery using CSF liquid biopsy or after surgery in brain specimens will likely be integrated in planning surgical strategies and reintervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Epilepsy/genetics , Molecular Targeted Therapy/methods , Precision Medicine/methods , Genetic Predisposition to Disease/genetics , Humans
20.
Nat Commun ; 12(1): 5655, 2021 09 27.
Article in English | MEDLINE | ID: mdl-34580292

ABSTRACT

High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients' leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.


Subject(s)
Antineoplastic Agents/pharmacology , Biomarkers, Tumor/genetics , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Reverse Genetics/methods , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/genetics , Adult , Animals , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/antagonists & inhibitors , Child , Female , Gene Silencing , Homeodomain Proteins/antagonists & inhibitors , Homeodomain Proteins/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Male , Mice , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid-Lymphoid Leukemia Protein/antagonists & inhibitors , Myeloid-Lymphoid Leukemia Protein/genetics , Oncogene Proteins, Fusion/antagonists & inhibitors , Oncogene Proteins, Fusion/genetics , Precision Medicine/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Xenograft Model Antitumor Assays
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