51 results about "Myeloid leukemia" 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 discloses a novel application of a known eIF5B inhibitor in treating acute myelogenous leukemia (AML). It is found for the first time that the eIF5B inhibitor has high toxicity to various AML cells, can inhibit proliferation of the various AML cells and induce differentiation of the AML cells, has no significant influence on normal hematopoietic stem / progenitor cells, and can be used for developing drugs for treating AML. The invention provides a theoretical basis for research and development of anti-AML drugs, opens up a new application of the eIF5B inhibitor, provides a brand new method for treating AML, and has a wide application prospect in the technical field of AML treatment.

Disclosed herein are embodiments of a method for treating a disease or condition in a subject, comprising administering to the subject, a pyrazole compound according to formula I.The compound may be administered as a composition, such as a spray-dried formulation. The disease or condition may be hidradenitis suppurativa, or a lymphoid neoplasm, and may be chronic myeloid leukemia or chronic myelomonocytic leukemia.

The invention discloses a staurosporine glucoside derivative as well as a preparation method and application thereof, and belongs to the field of medicine synthesis. C3-NHCH3 of staurosporine is subjected to glycosylation modification, and the staurosporine glycoside derivative shown in the formula (I) is prepared. The glycoside derivative prepared by the invention has a better inhibition effect on human acute myeloid leukemia cells THP-1, human bladder cancer cells 5637, human colon cancer cells HCT-116, human pancreatic cancer cells PATU8988T and human liver cancer cells HuH-7, and the compound 5 also has an excellent inhibition effect on human gastric cancer cells MKN-45. A candidate compound is provided for development of drugs for bladder cancer, colon cancer, pancreatic cancer, liver cancer, stomach cancer or acute myeloid leukemia.

The present invention relates to methods of treating leukemia using Tyrosine Kinase inhibitors. The invention particularly relates to methods of treating CML and ALL using a compound of Formula I or a pharmaceutically acceptable salt thereof. The compound of Formula 1 has been shown to be efficacious safe and tolerable at a dose from 10 mg to 210 mg.

This invention belongs to the field of biomedical technology, specifically relating to a culture reagent composition and method for organoids from hematologic malignancies. The invention first provides a reagent composition for culturing organoids from hematologic malignancies, including acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition includes a bone marrow microenvironment mimicking matrix reagent and a specific culture medium. Using the reagent composition of this invention, hematologic malignancies can be cultured efficiently with high survival rates. Furthermore, the bone marrow microenvironment mimicking matrix component used in this invention, compared to the commonly used Matrigel matrix in the field, allows for more accurate phenotypic differentiation of hematologic malignancies.

Disclosed in the present invention are a PIM kinase inhibitor as shown in general formula II, a pharmaceutical composition thereof, a preparation method therefor and the use thereof in the preparation of a drug for preventing and / or treating indications related to a PIM signaling pathway. The compound of the present invention is an ideal PIM kinase inhibitor with a high activity, which can be used for treating and / or preventing diseases including autoimmune diseases and tumors, e.g., inflammatory bowel disease, hematologic malignancies such as acute myeloid leukemia, myelofibrosis and chronic lymphocytic leukemia, and solid tumors such as gastric cancer and prostate cancer.

The invention discloses application of an LPIN1 inhibitor in preparation of drugs for treating FLT3-ITD mutant acute myelogenous leukemia, reducing tumor load of a patient with the FLT3-ITD mutant acute myelogenous leukemia, improving the survival rate of the patient with the FLT3-ITD mutant acute myelogenous leukemia and / or reducing the proliferation activity of primary cells of the patient with the FLT3-ITD mutant acute myelogenous leukemia. The LPIN1 inhibitor for inhibiting lipid metabolism related enzyme LPIN1 can significantly induce apoptosis of FLT3-ITD mutant AML cells, has limited influence on non-mutant AML cells, and has mutation specificity. More importantly, the LPIN1 inhibitor (such as propranolol) and the FLT3 inhibitor (such as quinatinib) are combined for use, so that a synergistic anti-leukemia effect can be generated, and a remarkable anti-tumor effect is shown in vitro and in a mouse transplantation tumor model, so that the LPIN1 inhibitor and the FLT3 inhibitor have a good application prospect.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma, or myelodysplastic syndrome by administration of Compound (I): (I), or a pharmaceutically acceptable salt thereof.

This invention relates to a method for constructing a prognostic assessment model for acute myeloid leukemia (AML) with NPM1 mutations. The method includes the following steps: (1) collecting and detecting gene mutation data required for the prognostic assessment system of AML patients with NPM1 mutations, including the mutation status of FLT3-ITD, IDH1, and SRSF2 genes; (2) assigning values ​​according to the mutation status of FLT3-ITD, IDH1, and SRSF2; (3) substituting the values ​​assigned in step (2) into the formula: mNPM1 AML risk score = 1.077 × FLT3-ITD - 0.800 × IDH1 + 1.512 × SRSF2, and performing grouped and parallel prognostic assessments on the calculated values. This invention provides a prognostic assessment model for AML with NPM1 mutations, providing important guidance for the treatment of such patients and having good clinical application value.

The present disclosure relates to RNAi agents useful in methods of treating KRAS-related diseases such as a proliferative disease, including without limitation a solid or liquid cancer, adenocarcinoma, colorectal cancer, advanced and / or metastatic colorectal cancer, colon cancer, lung, non-small cell lung cancer and lung adenocarcinoma, acute myelogenous lung, bladder, brain, breast, cervical, endometrial, gastric, head and neck, kidney, leukemia, myelodysplastic syndrome, myeloid leukemia, liver, melanoma, ovarian, pancreatic, prostate, testicular, thyroid cancers, and cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to KRAS.

This invention provides a method for preparing a non-natural humanized chimeric anti-human CD45RA antigen receptor, which specifically binds to the human CD45RA antigen by expressing CAR protein on T cells. Based on a humanized 3A4 antibody, this invention constructs a lentiviral expression vector pLenti / Hu3A4-4-1BB-3ζ. Compared with murine CAR, the humanized CAR significantly reduces immunogenicity, noticeably decreases the production of anti-scFv antibodies, and avoids the HAMA reaction. Research results show that Hu3A4CAR-T cells can specifically bind to the CD45RA-highly expressing myeloid leukemia cell line KG1a. Hu3A4CAR-T cells can target and kill 3A4-positive cell lines and leukemia cells, alleviate the human anti-mouse antibody response, and significantly reduce the production of anti-scFv antibodies, thereby ensuring the CAR's killing activity.

The invention provides a therapeutic response model for acute myelogenous leukemia (AML) accompanied with myelodysplastic syndrome related genetic abnormality (MRGA) and application thereof, a survival risk scoring model and application thereof, and the survival risk scoring model is constructed based on the lifetime, cytogenetics abnormality, gene mutation and clinical factors of a patient. Patients are divided into a low-risk group, a medium-risk group and a high-risk group through the model, the AUC value of the patients reaches 0.789-0.831 in the period of 1-3 years, and the clinical practicability of the model in the aspect of making AML treatment decisions based on myeloid associated dysplasia (MRGA) is proved through remarkable survival differences among different risk groups. In addition, a combined scoring system for the treatment response and lifetime of the MRGA AML patient is further developed, and a new technical support is provided for clinical decision-making of the MRGA AML.

The application provides a fluorescent probe for myeloperoxidase detection, and a preparation method and application thereof. The fluorescent probe can detect MPO in living cells, greatly shortens the detection time, has low production cost, high specificity, and can be fixed on the protein of the cell after response, thereby avoiding non-specific fluorescent signal transmission and reducing false positives in the detection process. Meanwhile, the fluorescent probe can realize the function of distinguishing myeloid leukemia cells from lymphoid leukemia cells.

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG / Il2rg KO / hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

An anti-IL1RL1 / IL-33 / NF-kB antibody and a method for treating acute myeloid leukemia using same. The anti-IL1RL1 / IL-33 / NF-kB antibody comprises an anti-IL1RL1 antibody, an anti-IL-33 antibody, and an anti-NF-kB antibody. The treatment method comprises: step 1, patient assessment and diagnosis; step 2, antibody selection and preparation; step 3, treatment plan formulation; step 4, antibody administration; step 5, efficacy monitoring and assessment; and step 6, subsequent treatment and follow-up. The combined use of the anti-IL1RL1 antibody, the anti-IL-33 antibody, and the anti-NF-kB antibody for treating AML can inhibit the proliferation and survival of AML cells at multiple levels by means of simultaneously blocking the IL-33 / IL1RL1 signaling pathway and NF-kB activation, thereby improving the therapeutic effect.

The application provides a use of vincristine and lithium carbonate as co-active ingredients in the preparation of a medicament for treating tumors. The vincristine and lithium carbonate as co-active ingredients of the application have a killing effect on various leukemia cells, including human acute lymphoblastic leukemia cell lines, chronic myeloid leukemia cells, acute monocytic leukemia cell lines; in particular, for human acute lymphoblastic leukemia cell lines, compared with single free drugs (lithium carbonate or vincristine), lithium carbonate and vincristine free drug combination, the leukemia cell proliferation can be more effectively inhibited; in addition, the vincristine and lithium carbonate as co-active ingredients of the application can obviously stimulate the generation of granulocyte colony-stimulating factor, and alleviate the neutropenia side effect caused by chemotherapy.

The application relates to the field of biological medicine, in particular to application of lysosome ion channel CLN7 as a target in preparation of a drug for treating myeloid leukemia. In K562 and other myeloid leukemia cell strains, the proliferation ability of leukemia cells is significantly inhibited after CLN7 expression is knocked down by using specific shRNA interference technology, and cell apoptosis is greatly promoted. Experiments prove that inhibition of CLN7 enhances lysosome degradation function, promotes degradation of leukemia-related pathogenic proteins, and blocks survival signal dependence of leukemia cells. Preliminary results show that the influence of inhibition of CLN7 on normal hematopoietic cells is significantly lower than that on leukemia cells, which indicates that the treatment window is good.

The invention discloses a polyketone-tropolone hybrid compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The structural formula of the polyketone-tropolone hybrid compound provided by the invention is as shown in the formula (I). The half inhibitory concentration (IC50) of the compound to human chronic myelogenous leukemia cells (K562) and human colorectal adenocarcinoma cells (HT-29) reaches a nanomole level in in-vitro antitumor activity evaluation; while the efficient anti-tumor activity is maintained, the compound has excellent tumor cell selectivity, and valuable candidate molecules are provided for research and development of novel anti-tumor drugs.

The invention provides a treatment response model for acute myelogenous leukemia (AML) accompanied with myelodysplastic syndrome related genetic abnormality (MRGA) and application thereof, and the model combines clinical data, cytogenetics and molecular biology data of patients. Variables significantly related to the complete remission rate of the patient are screened out through Lasso regression and Cox multivariable regression analysis, a treatment response model for predicting the complete remission rate is constructed based on the variables, and a combined scoring system formed by the treatment response model and a constructed survival risk scoring model is used for predicting the response of the patient to induced treatment and 1-3-year survival prognosis. And an individualized basis is provided for clinical treatment decision-making of the AML patient.

The application discloses a kit for detecting common fusion genes of myeloid leukemia based on a multiple digital PCR method, wherein specific primer probe combinations are adopted, and through an optimized 7-color multiple digital PCR technology platform, the kit can be used for rapid and accurate molecular detection of 46 common fusion genes of myeloid leukemia in clinic. The preferred primer probe combinations and detection systems disclosed by the application innovatively add a PCR enhancer into a PCR reaction liquid and innovatively construct a ROX+CY5 and Atto 425 (A425)+VIC double-channel detection system, the PCR enhancer significantly improves the efficiency and specificity of the multiple amplification system, and the double-channel system can realize accurate detection of 46 fusion genes in three detection holes. The application has the advantages of multiple accurate quantification, high sensitivity, strong specificity, strong anti-interference ability, good repeatability, simplicity and rapidness, high throughput, low cost and the like, has a good clinical application prospect, and can provide reference bases for rapid and accurate diagnosis, treatment, drug selection, efficacy evaluation and prognosis judgment of myeloid leukemia in clinic.

Disclosed herein are conditional siRNAs activatable by CBFβ-MYH11 oncogenic gene and use thereof for treating conditions such as acute myeloid leukemia (AML). The conditional siRNAs target MCL-1 or HDAC8.

The present invention relates to methods of treating acute myeloid leukemia with anti-CD38 antibodies.

This invention relates to the field of pharmaceutical technology, specifically to the application of *Citrus aurantium* in the preparation of antitumor drugs. The invention uses *Citrus aurantium* as a raw material to obtain, for the first time, extracts with antitumor activity and novel compounds with extremely high activity. Furthermore, it provides a new natural method for obtaining *Citrus aurantium* alkaloids A, B, C, and D. The extracts and isolated monomeric compounds can effectively inhibit the growth of various tumor cell lines in vitro, including human colorectal cancer cells, human chronic myeloid leukemia cell lines, human gastric adenocarcinoma cell lines, human small cell lung cancer cell lines, and human liver cancer cell lines. The obtained extracts and monomeric compounds target a wide range of cancer cells, exhibiting significant effects on various cancer cells, thus achieving therapeutic effects and showing broad application prospects.

To provide a pharmaceutical composition for treating acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS).SOLUTION: The present invention provides a pharmaceutical composition for use in a method for treating acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) in a subject, where the pharmaceutical composition comprises an anti-CD70 antibody and an antigen-binding fragment thereof. The method comprises administering to the subject one or more doses of the anti-CD70 antibody or antigen-binding fragment thereof, and administering to the subject azacitidine or decitabine.SELECTED DRAWING: None

This invention provides CD33-targeting CAR-gdT cells and their application in the treatment of acute myeloid leukemia. Specifically, this invention, through screening, provides CD33-CAR-γδT cells with high transfection efficiency, strong proliferative capacity, and efficient killing of target cells. This invention also provides a method for preparing CD33-CAR-γδT cells and their application in the treatment of acute myeloid leukemia.

The invention discloses a biomarker combination for predicting survival prognosis of an acute myeloid leukemia patient and application of the biomarker combination, and belongs to the technical field of molecular biomedicine. It is found for the first time that the specific N-sugar chain level in a blood sample during definite diagnosis of an AML patient is significantly related to survival prognosis. Through the screened N-carbohydrate chain marker, a Cox regression analysis is utilized to construct an AML prognosis prediction scoring system (AML-GPSS). According to the system, prognosis scores are obtained through a quantitative calculation formula, and patients are divided into different prognosis risk groups according to a preset critical value. The invention provides a brand-new prognosis prediction model based on a protein post-translational modification function, a detection sample is easy to obtain, and the method is stable; an important bioinformatics tool and a new clinical practice scheme are provided for making up for the defects of an existing cytogenetics layering system and achieving early-stage accurate risk layering and individualized treatment decision making of AML patients.

The invention provides a method for synthesizing anthracycline compounds for treating chronic myelogenous leukemia by an enzyme method. The two anthracycline compounds are 10-decarboxyl-13-deoxyerythromycin and 10-hydroxy-13-deoxyerythromycin. The invention further provides a preparation method of the anthracycline compounds for treating the chronic myelogenous leukemia. The invention discovers and verifies that the 10-decarboxyl-13-deoxyerythromycin and the 10-hydroxy-13-deoxyerythromycin have obvious activity of resisting human chronic myeloid leukemia cells for the first time. And compared with adriamycin, the inhibition activity is improved by about 15 and 20 times. Therefore, the compound has the outstanding potential of being developed into an efficient new-generation anthracycline anti-tumor drug, and provides a new candidate drug choice for leukemia treatment.