16 results about "RUNX1" patented technology

The invention belongs to the technical field of gene engineering, and particularly relates to a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of AML patients and application of ubiquitin specific protease 20 serving as a target spot in treating acute myelogenous leukemia. The invention provides a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of an AML patient and application of ubiquitin specific protease 20 as a target spot in treating acute myelogenous leukemia, USP20 is used as a super enhancer regulation gene, and the progress of the AML is promoted by combining with CTNNB1, ERG, ELF1 and RUNX1. The knock-down of the USP20 can significantly inhibit AML proliferation in vivo and in vitro. The wnt-beta-catenin pathway can be influenced by interfering the expression of the USP20 so as to influence the progress of AML (acute myeloid leukemia). And the inhibition effect of the inhibitor AS1517499 subjected to virtual screening on the growth of the AML cells is superior to that of a commercial inhibitor GSK2643943A of USP20.

The invention belongs to the technical field of disease model construction, and particularly relates to a construction method of a chronic myelogenous leukemia mouse model with conditional human EZH2 overexpression and RUNX1 knockout. According to the invention, a chronic myelogenous leukemia mouse transgenic mouse model with conditional human EZH2 overexpression and RUNX1 knockout is successfully constructed, the model is induced to be converted from a chronic stage to a sudden change stage, and particularly, the model is a transgenic mouse model which is positive in Lyz2-CreERT2 / EZH2 / RUNX1 and carries BCR-ABL and SCL-tTA. It is proved that a human EZH2 conditional overexpression and RUNX1 knockout chronic myelogenous leukemia mouse transgenic mouse model has feasibility and importance for research on conversion from CML CP to BC samples, and a molecular mechanism for conversion from chronic myelogenous leukemia to a sudden change stage is revealed for research. And a new animal model and a new research idea are provided for understanding of disease progression and development of a new treatment strategy.

The invention discloses a nucleic acid aptamer targeting RUNX1 protein and application thereof, and belongs to the technical field of biology, the nucleotide sequence of the nucleic acid aptamer is shown as RUNX1-5, and the nucleic acid aptamer is obtained through an in-vitro screening SELEX (systematic evolution of ligands by exponential enrichment) technology. The nucleic acid aptamer is small in molecular weight, is easy to chemically synthesize and functionally modify, has good physical and chemical stability, shows high affinity to the RUNX1 protein, has a dissociation constant lower than 30 nM, has good application prospects in the aspects of detection, separation and purification, marking and the like of the RUNX1 protein, and can also be used for preparing medicines for treating RUNX1 related diseases.

Pharmaceutical compositions and compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized an RNA aptamer are useful in methods of treating cancer (such as leukemia) and methods of inhibiting DNA methyltransferase. In embodiments, the RNA aptamer binds to an intracellular target such as DNMT1, NF-kB, RUNX1, MYC, MYB, ETS, PAX5, MDM2, F0XM1, PU.l, STAT3, STATS. STAT6, FAD, ATP5B, or beta-catenin.

The application belongs to the technical field of biological pharmacy, and provides a set of esophageal cancer methylation early screening markers and application thereof, the markers being any one or a combination of two or more of ZNF693, MMP14, JAG1, RUNX1 or NOTCH1 gene sequences or gene fragments containing at least one CpG methylation site; the application also discloses application of the set of biomarkers in preparation of a detection kit for diagnosing and / or evaluating the methylation degree of esophageal cancer or in screening of drugs for treating and / or relieving esophageal cancer. The application can effectively identify cancer patients by quantifying the dynamic change of the methylation level, and reduce the risk of missed detection caused by tumor heterogeneity; by establishing a high-throughput and standardized detection process, the application can provide a precise molecular typing tool for early intervention of esophageal cancer; the application overcomes the limitations of traditional technology, such as insufficient detection sensitivity for early cancer and dependence on invasive operation, and can promote clinical transformation of "early screening and early diagnosis".

This invention discloses a risk stratification assessment model, device, and construction method for RUNX1::RUNX1T1-positive children with acute myeloid leukemia. The construction method includes: acquiring sample clinical data; assessing the correlation between clinical predictors and overall survival (OS) and event-free survival (ORS); for continuous variables, determining the optimal risk cutoff value for predicting poor prognosis; converting the continuous variables into binary variables; performing univariate Cox proportional hazards regression analysis to screen for factors significantly associated with OS and ORS; and incorporating these factors into a multivariate Cox proportional hazards regression model to confirm independent prognostic factors. This invention systematically integrates the clinical variable MRD1 and the percentage of peripheral blood blasts at diagnosis as core predictors, constructing a model capable of accurately assessing ORS. + A prognostic model for pAML risk was developed and rigorously validated. This model demonstrated superior predictive performance, effectively and accurately identifying patients with a high actual risk of relapse and death from the traditionally low-risk patient population.

Provided herein are methods and compositions for differentiating induced pluripotent stem cells into granulosa-like cells by overexpressing transcription factors such as NR5A1 and a RUNX family protein (e.g., RUNX1 and / or RUNX2).

The invention provides a primer probe group for detecting three leukemia fusion genes BCR-ABL1, ETV6-RUNX1 and TCF3-PBX1 and application of the primer probe group, and establishes a method for simultaneously detecting RNA of the three fusion genes based on capture and ligation reaction combined with multiple fluorescent quantitative PCR. The primer probe group comprises a capture probe, a connection probe, an amplification primer and a Taq-Man probe which are respectively used for detecting multiple types and reference genes of three fusion genes. Nucleic acid extraction and reverse transcription are not needed, target RNA in whole blood, dried blood spots or bone marrow samples can be directly split and captured, and three fusion genes are simultaneously detected in the same fluorescent quantitative PCR reaction system. The detection sensitivity is that the copy / reaction of BCR-ABL1 is 75, the copy / reaction of ETV6-RUNX1 is 6, and the copy / reaction of TCF3-PBX1 is 29.

The invention belongs to the technical field of mouse model construction, and particularly relates to a construction method of a chronic myelogenous leukemia mouse model with RUNX1 gene conditional knockout. The method comprises the following steps: hybridizing a RUNX1 gene conditional knockout mouse and an LYZ2-CreERT2 mouse to obtain an F1 generation, and carrying out DNA (Deoxyribose Nucleic Acid) identification and screening to obtain a double-transgenic mouse with the genotype of LYZ2-CreERT2 / RUNX1; then hybridizing the LYZ2-CreERT2 / RUNX1 double-transgenic mouse of the F1 generation with the SCL-tTA / Bcr-abl double-transgenic mouse to obtain an F2 generation, and carrying out DNA (Deoxyribose Nucleic Acid) identification and screening to obtain a four-transgenic mouse of which the genotype is SCL-tTA / Bcr-abl / LYZ2-CreERT2 / RUNX1. The invention provides a solid research basis for deep research of the effect of the RUNX1 gene in chronic myelogenous leukemia and research and development of LSCs targeted drugs aiming at the RUNX1 gene.

The application provides an application of auro-thio-pan in preparation of a drug for treating a USP6 gene rearrangement and abnormal activation disease, and the auro-thio-pan is a lipophilic gold-based compound. Researches of the application show that in addition to the USP6 gene rearrangement disease, tumors such as osteosarcoma, RUNX1 gene rearrangement and CBFbeta gene rearrangement leukemia, synovial sarcoma and the like also have abnormal activation of USP6, and are clinical application scenarios of USP6 inhibitors. It is further found that the compound auro-thio-pan can effectively combine with a catalytic domain of USP6 and inhibit the deubiquitination enzyme activity of USP6, and inhibit the growth of RUNX1 rearrangement tumors at the cell and animal levels. The application opens up a new direction for the development of a drug for treating the USP6 gene rearrangement and abnormal activation tumor and the like, and expands the application range of auro-thio-pan in the treatment of clinical diseases, and provides a possibility for improving the prognosis and survival of corresponding clinical disease patients.

Provided herein are compounds, compositions, and methods for lowering expression levels of runt-related transcription factor 1 (RUNX1) in a cell, tissue or animal. Further provided are methods of improving memory and cognitive functioning in individuals with Down syndrome (DS) using an antisense compound targeted to a RUNX1 nucleic acid. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of decreasing inflammation and slowing cognitive decline in individuals with dementia.

The invention relates to the field of cancer, in particular breast cancer. In particular it relates to the field of immune system directed approaches for tumor reduction and control. Some aspects of the invention relate to vaccines, vaccinations and other means of stimulating an antigen specific immune response against a tumor in individuals. Such vaccines comprise neoantigens resulting from frameshift mutations that bring out-of-frame sequences of the GATA3, CDH1, MAP3K1, RUNX1, and TP53 genes in-frame. Such vaccines are also useful for ‘off the shelf’ use.

Described herein are methods for treating and reducing risk of fibrosis, e.g., pulmonary fibrosis, in a subject by administering an inhibitor of RUNX family transcription factor 1 (RUNX1) or core-binding factor subunit beta (CBFβ), e.g., in a subject who has a viral infection.

Provided are: a method for producing CD4-positive T cells, which comprises a step for knocking out one or more genes selected from the group consisting of RUNX3, ZBTB7B, SOCS1, SOCS3 and GIMAP5 and / or overexpressing the RUNX1 gene from human induced pluripotent stem cells (iPSC); a CD4-positive T cell that can be obtained by the method; and a pharmaceutical composition such as an immunotherapeutic agent that contains the CD4-positive T cell.

The invention discloses a ZNF292:: PNRC1 fusion protein and an application of the ZNF292:: PNRC1 fusion protein as a tumor marker. The DNA sequence of the fusion gene is as shown in SEQ ID NO.1, and the amino acid sequence of the coded fusion protein is as shown in SEQ ID NO.2. According to the invention, the fusion gene is identified for the first time in children with recurrent and refractory AML through high-throughput sequencing, and it is proved that the fusion gene promotes leukemia progression by destroying the cancer inhibition function of PNRC1. Specific PCR primers (SEQ ID NO: 3-4) can accurately detect the fusion gene, and the fusion gene is significantly related to a higher MRD level and poorer prognosis. Importantly, when the fusion gene coexists with classical carcinogenic fusion genes such as RUNX1: RUNX1T1 and the like, prognosis of a patient can be synergistically worsened. The invention provides a new molecular marker and risk stratification index for children AML, and has important value for accurate diagnosis and individualized treatment.

The present application relates to the application of spermidine in the preparation of drugs for treating leukemia, which is specific to the loss-of-function mutation of Runx1 in acute myeloid leukemia (AML) patients, and induces apoptosis of AML cells by spermidine.