36 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 an acute myelogenous leukemia cell strain with multiple adverse prognostic gene mutations in human and application thereof, the cell strain is named as human acute myelogenous leukemia cell strain YYXY-M14 and preserved in China Center for Type Culture Collection (Wuhan University, Wuhan, China) on October 12, 2024, and the preservation number is CCTCC NO: C2024350. The acute myelogenous leukemia cell strain simultaneously has three acute myelogenous leukemia poor prognostic gene mutations of TP53, RUNX1 and ASXL1, has the in-vitro natural proliferation capacity of acute myelogenous leukemia cells, and can be used as a cell material for researching the pathogenic mechanism of human acute myelogenous leukemia with positive mutation of human TP53, RUNX1 and ASXL1 in vitro. Meanwhile, the method can be used for in-vivo animal model construction and acute myelogenous leukemia drug screening and evaluation research.

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.

The invention belongs to the technical field of cancer suppression methods, and discloses application of inhibiting RUNX1 in controlling the progress of non-small cell lung cancer. The expression quantity of Mig6 is improved by inhibiting RUNX1, so that EGFR is inhibited, and the development of cancer cells is further inhibited. According to the invention, Chb-M'is used for antagonizing RUNX1 so as to inhibit RUNX1. The Mig6 can inhibit phosphorylation of EGFR (epidermal growth factor receptor) and induce cell apoptosis. According to the invention, the relation mechanism of RUNX1 and Mig6 in EGFR wild type NSCLC is clarified, and the effectiveness of RUNX1 inhibition as a new treatment strategy of EGFR wild type NSCLC is researched.

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".

The invention belongs to the technical field of gene detection, and particularly relates to a probe library and a method for detecting systemic mastocytosis gene mutation, the probe library completely covers probe combinations of gene sequences corresponding to a target area, and the gene mutation sequences comprise exon probe combinations for detecting ASXL1, ATM, CBL, DNMT3A, ETV6, EZH2, IDH1, IDH2, JAK2, KIT, KRAS, NRAS, RUNX1, SETBP1, SF3B1, SMC3, SRSF2, TET2, TP53 and U2AF1; the probe library can be used for simultaneously detecting the multi-gene multi-site mutation of the systemic mastocytosis, and the detection method can be used for comprehensively screening the mutation of a plurality of genes related to the diagnosis and treatment of the systemic mastocytosis.

The invention belongs to the technical field of biological medicines, and provides application of CDCA7 and RUNX1 in screening of drugs for promoting macrophage infiltration in an esophageal squamous cell carcinoma immune microenvironment. The CDCA7 is low in expression, the RUNX1 is low in expression, and immune cell infiltration in an ESCC immune microenvironment is promoted. Experimental results show that the CDCA7 positively regulates the transcriptional level of the RUNX1, and the RUNX1 negatively regulates the transcriptional level of the CCL5, so that the CDCA7 indirectly negatively regulates the expression level of the CCL5. After the expression level of CDCA7 is increased, the expression level of CCL5 is reduced, and the chemotactic effect on macrophages, especially M0 and M1 type macrophages, is reduced, so that the infiltration of the M0 and M1 type macrophages is reduced. The CDCA7 can regulate and control the expression level of RUNX1 through transcription and indirectly influence the expression level of a chemotactic factor CCL5, so that the chemotactic effect of macrophages in a tumor microenvironment, especially M1 type macrophages, is influenced.

The invention provides an application of Jinnofen in preparation of a medicine for treating USP6 gene rearrangement and abnormal activation diseases. The Jinnofen is a lipophilic gold-based compound. The research shows that besides USP6 gene rearrangement diseases, tumors such as osteosarcoma, RUNX1 gene rearrangement and CBF beta gene rearrangement leukemia, synovial sarcoma and the like have USP6 abnormal activation, and the USP6 inhibitor is a clinical application scene of the USP6 inhibitor. It is further found that the compound Jinnofen can be effectively combined with a USP6 catalytic structural domain, inhibit USP6 deubiquitination enzyme activity and inhibit growth of RUNX1 rearrangement type tumors in the cell and animal level. The invention opens up a new direction for research and development of drugs for treating diseases such as USP6 gene rearrangement and abnormally activated tumors at present, also expands the application range of Jinnofen in clinical disease treatment, and provides possibility for improvement of prognosis and survival of patients with corresponding clinical diseases.

The invention provides an RUNX1:: QSER1 fusion gene and an application thereof in leukemia, and mainly relates to an application in preparation of RUNX1:: QSER1 fusion gene positive leukemia diagnosis and treatment products. The fusion gene is formed by fusing exons 1-6 of the RUNX1 gene and exons 2-5 of the QSER1 gene. According to the fusion gene, abnormal high expression of the QSER1 gene is caused by a promoter replacement mechanism, and overexpression of RUNX1: QSER1 significantly enhances the proliferation ability and clone formation ability of cells, and promotes leukemia cell proliferation and chemotherapy resistance. The invention provides a RUNX1:: QSER1 fusion gene and fusion protein as markers for leukemia diagnosis and typing, prognosis evaluation and individualized treatment, and as a target for clinical drug treatment, the RUNX1:: QSER1 fusion gene and fusion protein are used as markers for leukemia diagnosis and typing, prognosis evaluation and individualized treatment. New possibility is provided for precise diagnosis and treatment of leukemia, and the kit can be widely applied to clinical prognosis evaluation and individualized treatment.

The present invention relates to a somatic cell nuclear transfer method and its application. This method uses a haploid embryonic stem cell system to obtain donor somatic cells in which one or more of 26 imprinted genes related to H3K27me3 are knocked out monoallelically. The results show that monoallelic knockout of one or more of Slc38a2, Slc38a4, Sfmbt2, Etv6, Platr4, Gramd1b, Slc38a1, Gab1, Mbnl2, Smoc1, Bmp7, Rbms1, Fam198b, Sh3gl3, Hunk, Jade1, E2f3, Tle3, Runx1, Epas1, Bbx, Enc1, Inhbb, Sox21, Otx2, Rbp2 (such as one or more of the four genes Sfmbt2, Jade1, Gab1, and Smoc1) with H3K27me3 makes the imprinted expression patterns of these genes tend to be normal. At the same time, cloning using these donor somatic cells can increase the somatic cell cloning efficiency to 14%, while the somatic cell cloning efficiency of the wild-type control group is 0. In addition, for the cloned animals obtained by this method, the phenomenon of large placenta - large fetus is corrected.

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.

The present invention discloses a human acute myeloid leukemia cell line with normal karyotype and its use. The human acute myeloid leukemia cell line with normal karyotype is named as human acute myeloid leukemia cell line YYXY-M4, which was deposited in China Center for Type Culture Collection (Wuhan University, Wuhan, China) on July 24, 2023, with a deposit number of CCTCC NO: C2023217. The present invention obtains mononuclear cells by extracting and separating peripheral blood separated by a blood cell separator from a patient with normal AML karyotype, and obtains them by continuous natural passage in vitro culture. The leukemia cell line has a normal karyotype and is accompanied by mutations in FLT3, RUNX1, ASXL1, and IDH1. Good in vitro proliferation ability can be used as a cell material for studying the occurrence and development mechanism of human acute myeloid leukemia with normal human karyotype and in vitro research on individualized treatment, and can also be used for in vitro and in vivo research on drug screening and evaluation of human acute myeloid leukemia with normal human karyotype, and guide clinical medication.

The invention belongs to the technical field of biological pharmacy, and provides a group of esophageal cancer methylation early screening markers and application thereof, the group of markers is any one of ZNF693, MMP14, JAG1, RUNX1 or NOTCH1 gene sequences or gene segments containing at least one CpG methylation site, or a combination of any two or more of the ZNF693, MMP14, JAG1, RUNX1 or NOTCH1 gene sequences or gene segments containing at least one CpG methylation site; the invention also discloses an application of the group of biomarkers in preparation of a detection kit for diagnosing and / or evaluating the methylation degree of esophageal cancer or an application of the group of biomarkers in screening of drugs for treating and / or relieving esophageal cancer. According to the method, by quantifying the dynamic change of the methylation level, cancer patients can be effectively identified, and the risk of missing detection caused by tumor heterogeneity is reduced; by establishing a high-throughput and standardized detection process, a precise molecular typing tool can be provided for early intervention of esophageal cancer; the limitation that the traditional technology is insufficient in early canceration detection sensitivity and depends on invasive operation is overcome, and the clinical transformation of early screening and early diagnosis can be promoted.

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).

Familial Platelet Disorder (FPD) is associated with germline RUNX1 mutations, establishing a preleukemic state and increasing the risk of developing acute leukemia. Conventional approaches lack intervention strategies that may delay or prevent leukemia progression in patients. The present disclosure integrates single-cell transcriptomics, flow cytometry, and spatial proteomics data analyses for a large cohort of FPD patient samples to show that RUNX1 mutations unleash inflammatory signaling in familial platelet disorder. Specifically, the receptor CD74 has been identified as a biomarker and a master regulator of downstream signaling pathways. Embodiments of the present disclosure provide diagnostic and treatment methods for FPD in patients.

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.

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 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 provides ocular formulations and features a nano-emulsion composition, e.g., a nano-emulsion comprising a CBFβ-RUNX1 inhibitor. The composition comprises a particle with a length of less than 200 nanometers in at least one dimension.

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.

Heterocyclic compounds of Formula I:and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and / or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NK), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and / or abnormal chromosome (5 / 7), and / or a high leukemic stem cell (LSC) frequency.

The invention discloses a combined gene kit for second-generation sequencing of hereditary thrombocytopenia, application of the combined gene kit and a sequencing method based on the combined gene kit, and belongs to the field of clinical application of a second-generation gene sequencing technology. The combined gene detection kit covers all exons and untranslated regions of 51 main pathogenic genes and 21 potential pathogenic genes, so that the mutation detection rate and the diagnosis accuracy are remarkably improved; detection of various thrombocytopenia related mechanism genes is newly added, and mutation in a non-hotspot region of the gene, especially pathogenic sites in a 5 '-UTR region, can be found. By detecting specific genes such as GATAl, MYH9, RUNX1 and the like, the hereditary thrombocytopenia can be accurately diagnosed, misdiagnosis is effectively avoided, early diagnosis of diseases is realized, and a basis is provided for formulating a personalized treatment scheme; in addition, the method can also identify new genetic variation or prognosis related gene mutation, detect carriers of recessive genetic disease virulence genes, contribute to reduction of genetic disease risks and have remarkable clinical application value and technical advantages.

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.