31 results about "Acute myelogenous leukemia (AML)" patented technology

The present invention is directed to methods for establishing a composite marker profile for a sample derived from an individual suspected having a neoplastic condition. A composite marker profile of the invention allows for identification of prognostically and therapeutically relevant subgroups of neoplastic conditions and prediction of the clinical course of an individual. The methods of the invention provide tools useful in choosing a therapy for an individual afflicted with a neoplastic condition, including methods for assigning a risk group, methods of predicting an increased risk of relapse, methods of predicting an increased risk of developing secondary complications, methods of choosing a therapy for an individual, methods of determining the efficacy of a therapy in an individual, and methods of determining the prognosis for an individual. In particular, the method of the present invention discloses a method for establishing a composite marker profile that can serve as a prognostic indicator to predict whether the course of a neoplastic condition in a individual will be aggressive or indolent, thereby aiding the clinician in managing the patient and evaluating the modality of treatment to be used. In particular embodiments disclosed herein, the methods of the invention are directed to establishing a composite marker profile for a leukemia selected from the group consisting of Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), and Acute Lymphocytic Leukemia (ALL).

The invention relates to a combined reagent for detecting acute myelocytic leukemia cells and a system thereof, wherein the combined reagent and the system thereof belong to the field of medical technology. The combined reagent comprises at least one selected from the following antibody combinations: a first antibody combination which comprises CD38, CD13, CD34, CD117, CD33, CD19, HLA-DR and CD45antibodies; a second antibody combination which comprises CD38, CD64, CD34, CD123, CD56, CD14, HLA-DR and CD45 antibodies; and a third antibody combination which comprises CD38, CD7, CD34, CD5, CD11b,CD15 and CD45 antibodies. The antibody combinations of the invention cover the expression marks of three systems of granulocyte, single cell and lymphocyte. A normal antibody expression mode is established. Tumor cells can be identified maximally. Furthermore, through a large number of experiment data, the antibodies in each combination have no problem of mutual expression inhibition. FurthermoreAML-MRD can be comprehensively and quickly detected with high sensitivity through multi-parameter flow type cell analysis.

The invention is in the field of molecular medicine and provides methods for the treatment of acute myeloid leukemia. These methods are based on the observation that microRNA-9 and microRNA-9* are involved in the pathogenesis of the disease in that the overexpression of microRNA-9 / 9* block myeloid differentiation in vitro. More in particular, microRNA-9 / 9* were found to play a role in leukemic transformation in acute myeloid leukemia.

Belonging to the field of pharmaceutical compounds, the invention relates to 11, 20-dicarbonyl Jiyuan rubescensin a and L-amino acid-14-ester trifluoroacetate thereof, and a preparation method and usethereof. The preparation method includes: adopting Jiyuan rubescensin a as the raw material and performing oxidation with a Jones reagent, thus obtaining 11, 20-dicarbonyl Jiyuan rubescensin a, the structure of which is shown as the specification; then carrying out 14-position esterification reaction with N-BOC-L-amino acid to obtain N-BOC-L-amino acid-11, 20-dicarbonyl Jiyuan rubescensin a ester(III), then removing BOC protective group in trifluoroacetic acid, and then conducting salt forming to obtain L-amino acid-14-(11, 20-dicarbonyl Jiyuan rubescensin a)ester trifluoroacetate, which hasthe following general formula. The compound has good stability and anti-tumor activity, and provides the basis for screening antitumor drugs against esophageal cancer, gastric cancer, primary liver cancer, pancreatic cancer, cardiac carcinoma, colorectal cancer, bladder cancer, breast cancer, acute myelogenous leukemia and the like.

The invention discloses a chimeric antigen receptor and a gene and a recombinant expression vector thereof, an engineered CD33 targeting NKT cell and an application thereof. The chimeric antigen receptor is CD33ScFv-CD8-CD137-CD3zeta which is formed by connecting CD33ScFv, a hinge domain and a transmembrane domain of CD8, an intracellular signal structural domain of CD137 and an intracellular signal structural domain of CD3zeta in series. By adopting the chimeric antigen receptor CD33ScFv-CD8-CD137-CD3zeta modified NKT cell for treating CD33 positive acute myelogenous leukemia in a progressive stage, drug resistance and chemotherapy resistance caused by combined application of a CD33 monoclonal antibody and chemotherapy can be effectively avoided, and the cell has specific killing activity on leukemia cells.

Myelodysplastic syndromes display both hematological and biological heterogeneity with variable leukemia potential. To determine whether microRNAs expression offers diagnostic discrimination or influences malignant potential in MDS, bone marrow miRNA expression was investigated from prognostically distinct MDS subsets using a microarray platform. After background subtraction and normalization, data were analyzed indicating thirteen miRNA signature with statistically significant differential expression, including down-regulation of members of a leukemia associated miRNA family. A unique signature consisting of 10 miRNAs was closely associated with International Prognostic Scoring System risk category permitting discrimination between lower and higher risk disease. Selective overexpression of miRNA-181 family members was detected in higher risk MDS, indicating pathogenetic overlap with acute myeloid leukemia. Analysis of miRNA expression profile offers diagnostic utility, and provides pathogenetic and prognostic discimination in MDS.

The invention relates to a micro ribonucleic acid (miRNA) marker group related to acute myelogenous leukemia, and a specific primer and application of the miRNA marker group. The marker group is composed of a miR-23b-3p marker and a miR-26a-5p marker, wherein a nucleotide sequence of the miR-23b-3p marker is as shown in SEQ ID NO.1, and the nucleotide sequence of the miR-26a-5p marker is as shown in SEQ ID NO.2. The invention also relates to a specific primer and application of the miRNA marker group. Two markers screened by the micro ribonucleic acids (microRNAs) marker group provided by the invention are strong in complementarity. Thus, the detection is quantitative and accurate, and the sensibility and the specificity of disease diagnosis are greatly improved.

The invention provides a CLL1 and CD33 double-target chimeric antigen receptor and application thereof. The chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, and the antigen binding domain comprises an anti-CLL1 single-chain antibody and an anti-CD33 single-chain antibody. According to the constructed CAR molecule simultaneously targeting CLL1 and CD33, the effect of comprehensively targeting acute myelogenous leukemia cells is achieved, the CAR-T cells for expressing CLL1 and CD33 double-target CAR are remarkable in tumor removal effect, the antigen escape phenomenon is avoided, and the CAR molecule has important significance in the field of tumor treatment.

The invention particularly relates to application of METTL3 in AML chemotherapy drug resistance, and belongs to the technical field of molecular biology and medicine. The clinical treatment effect of AML is poor, the prognosis condition is poor, and relapse and refractory cases cannot be relieved through conventional therapy. The invention provides a molecular marker for detecting the chemotherapy sensitivity of acute myelogenous leukemia by analyzing the expression difference of METTL3 in bone marrow of a patient relatively sensitive to AML chemotherapy and a patient resistant to AML chemotherapy. Through AML chemotherapy sensitive cell strains, chemotherapy drug-resistant cell strains and animal models, the AML chemotherapy drug-resistant treatment effect of the METTL3 inhibitor is proved. The research of the invention also proves that METTL3 can mediate AML chemotherapy resistance by regulating AML cell homing.

The invention discloses development and applications of a new human gene FAMLF in human gene recombination, malignant tumor gene detection and a specific monoclonal antibody, wherein, the new human gene FAMLF comprises cDNA of the new gene related to familial acute myelogenous leukemia and a polynucleotide sequence for completely opening a reading frame; the gene comprises a cDNA full-length sequence, wherein, the sequence table code thereof is SEQ ID No:1; and the sequence for completely opening the reading frame, wherein, the sequence table code thereof is SEQ ID No:2. The gene sets up the foundation for a diagnosis antibody, a protein chip, a gene chip and a gene medicine of the specific gene of leukemia in the future, thus playing an important role in developing and researching the new anti-leukemia medicine, improving diagnosis accuracy and treatment effect of leukemia and improving recovery rate of leukemia in Fujian province, and having potentially significant social and economic benefits. The invention lays the foundation for gene diagnosis and gene treatment of leukemia and other malignant tumors.

The invention provides a combined pharmaceutical composition for treating acute myelogenous leukemia and application of the combined pharmaceutical composition. The combined pharmaceutical composition for treating acute myelogenous leukemia comprises chidamide and apatinib. According to the combined medicine composition, the medicine chidamide and the medicine apatinib are creatively combined to serve as a medicine for treating acute myelogenous leukemia, and the research shows that the combined chidamide and apatinib have the effect of more remarkably inhibiting AML cell proliferation compared with single chidamide or apatinib; has the effect of more remarkably inducing AML cell apoptos compared with single chidamide or apatinib, and has the effect of more remarkably prolonging the survival time of an AML mouse model compared with single chidamide or apatinib. The combined pharmaceutical composition provides a new strategy and thought for the treatment of acute myelogenous leukemia, and has very significant significance.

The invention discloses a primer probe set, kit and method for quantitative detection of an expression level of a small integral membrane protein 3 (SMIM3) gene. The primer probe set comprises a component A and a component B; the component A includes a forward primer SMIM3-FP, a reverse primer SMIM3-RP and a probe SMIM3-probe; and the component B includes a forward primer ABL1-FP, a reverse primerABL1-RP and a probe ABL1-probe. The primer probe set, the kit and the method have the advantages that quantitative detection of the relative expression level of the SMIM3 gene in a cell is realized;moreover, the sensitivity of the SMIM3 gene and the sensitivity of an ABL1 gene both reach up to 100 copies; the sensitivity is high, results are accurate, and the reliability is high; a new auxiliarydiagnosis method or auxiliary identification method is provided for hematologic tumor cells (especially acute myelogenous leukemia and acute lymphoblastic leukemia); and the primer probe set, the kitand the method have broader application prospects.

The invention provides a chimeric antigen receptor combined anti-tumor medicine composition, a chimeric antigen receptor comprises a single-chain antibody ScFv capable of recognizing phosphatidylserine on the surface of a tumor cell, and an anti-tumor medicine is a chemotherapeutic medicine capable of increasing expression of phosphatidylserine on the surface of a tumor cell line or a primary tumor cell. The chimeric antigen receptor taking phosphatidylserine as a target spot is used for modifying immune cells, and the modified immune cells can be used for treating tumors with positive phosphatidylserine on the surface and particularly have a remarkable tumor killing effect on ewing sarcoma, acute lymphoma / leukemia, acute myelogenous leukemia and breast cancer.

The invention provides a compound with a structure as shown in a general formula (I), a deuterated substance, a stereoisomer or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound and application of the compound and the deuterated substance, the stereoisomer or the pharmaceutically acceptable salt. The compound provided by the invention has a good PIM kinase inhibition effect, is a novel, high-activity and low-toxicity ideal PIM inhibitor, can be used for treating and / or preventing diseases such as hematoma such as acute myelogenous leukemia, myelofibrosis and chronic lymphocytic leukemia, solid tumors such as gastric cancer and prostate cancer, and has a wide application prospect.

The invention belongs to the field of chimeric antigen recipient cells, and relates to a chimeric antigen recipient cell targeting human CD33 and NKG2DL as well as a preparation method and application thereof, and the chimeric antigen recipient cell contains amino acid sequences targeting binding human CD33 and targeting binding human NKG2DL. The immune response cell modified by the bispecific chimeric antigen receptor targeting CD33 and NKG2DL can enhance the combination with tumor cells, and has obvious anti-tumor activity in tumors expressing human CD33 / NKG2DL antigens, such as acute myelogenous leukemia (AML).

The invention discloses an application of isoliensinine in preparation of drugs for treating leukemia, the structure of isoliensinine is as shown in formula (1), and the leukemia comprises acute myelogenous leukemia, chronic granulocytic leukemia, T-cell malignant tumor and diffuse large B-cell lymphoma.

The invention relates to a micro ribonucleic acid (miRNA) marker group related to acute myelogenous leukemia, and a specific primer and application of the miRNA marker group. The marker group is composed of a miR-23b-3p marker and a miR-26a-5p marker, wherein a nucleotide sequence of the miR-23b-3p marker is as shown in SEQ ID NO.1, and the nucleotide sequence of the miR-26a-5p marker is as shown in SEQ ID NO.2. The invention also relates to a specific primer and application of the miRNA marker group. Two markers screened by the micro ribonucleic acids (microRNAs) marker group provided by the invention are strong in complementarity. Thus, the detection is quantitative and accurate, and the sensibility and the specificity of disease diagnosis are greatly improved.

The invention discloses an application of GNF-7 in preparation of an FLT3 mutant inhibitor. The GNF-7 provided by the invention can be in targeted combination with FLT3-ITD and F691L, overcomes drug-resistant mutation of F691L, achieves a better treatment effect on acute myelogenous leukemia compared with quinatinib AC220, and has a good application prospect.

The invention provides an application of a PI3K inhibitor in preparation of a drug for treating drug resistance to an FLT3 inhibitor, and the PI3K inhibitor can inhibit an excessively activated PI3K-Akt pathway so as to generate a stronger killing effect on acute myelogenous leukemia cells which are resistant to the FLT3 inhibitor.

The invention relates to the field of biological information, in particular to a method and system for completing karyotype analysis of a to-be-detected sample based on whole genome sequencing and a computer readable medium. The method for determining the predetermined chromosome variation of the to-be-detected sample replaces traditional karyotype analysis, second-generation sequencing and dynamic cutoff are combined, CNV large fragments can be rapidly and accurately detected, and meanwhile, according to the result, based on chromosome karyotype analysis, the detection accuracy of the CNV large fragments is greatly improved. Diseases (such as acute myelogenous leukemia and myelodysplastic syndrome) related to chromosome copy number variation can be detected, and treatment and prognosis can be guided. The detection method provided by the invention is high in sensitivity, lower in detection limit and more accurate in detection result, and can be used for prognosis of diseases related to chromosome copy number variation by annotating the position of the gene related to prognosis and the position of variation on the chromosome.

The invention relates to the field of new application of medicines, in particular to application of a small molecule compound Chelidonine in preparation of a medicine for treating acute myelogenous leukemia (AML) with FLT3-ITD mutation. In the invention, chelidonine is used for inhibiting MV4 of FLT3-ITD mutation in vitro; 11 cell proliferation and apoptosis induction can be realized, and the FLT3-ITD mutant AML can be targeted to act on FLT3-ITD mutant AML. In in-vivo experiments, the polypeptide can reduce the proportion of bone marrow hCD45 + cells, reduce the infiltration of bone marrow and spleen, increase the expression of liver and spleen apoptosis protein Caspase3 and prolong the survival time of NSG mice, has an in-vivo anti-tumor effect, can be used as a new means for FLT3-ITD mutated AML drug intervention, and brings a new hope to treatment of FLT3-ITD mutated AML.

The invention provides a tumor screening kit based on blood analysis, and relates to the technical field of blood detection. The tumor screening kit based on blood analysis comprises a staining enhancement solution for enhancing the staining effect and a specific antibody with a fluorescent staining mark, and the staining enhancement solution is prepared from the following raw materials in percentage by mass: 1%-5% of a surfactant, 90%-94% of a biological buffer solution and 0.5%-0.8% of polyethylene glycol. The leukocyte and the residual erythrocyte can be removed at one time, the enrichment efficiency is higher, interference of other cells on fluorescent staining can be eliminated after enrichment treatment, better observation through a fluorescence microscope is facilitated, expression on the surfaces of most acute myelogenous leukemia cells is achieved, and the application prospect is wide. The targeted CD20 antibody is a bispecific antibody taking a red blood cell surface antigen CD3 and a white blood cell surface antigen CD20 as targets, adapts to the heterogeneity of cells, and avoids the condition of leak detection.

The present invention discloses a primer probe set, a kit and a method for quantitatively detecting expression amount of GNA15 gene. The primer probe set includes components A and components B, the components A comprise an upstream primer GNA15-FP, a downstream primer GNA15-RP and a probe GNA15-probe, and the components B comprise an upstream primer ABL1-FP, a downstream primer ABL1-RP and a probeABL1-probe. Advantages are as follows: the method can quantitatively detect the relative expression amount of the GNA15 gene in cells, has sensitivity of GNA15 and sensitivity of ABL1 both up to 100copies, is high in sensitivity, accurate in results, and high in reliability, provides a new auxiliary diagnostic method or an auxiliary identification method for hematologic tumor cells (especially acute myelogenous leukemia and acute lymphoblastic leukemia) and has relatively great application prospects.

The invention belongs to the field of molecular therapy and particularly relates to an IDH2 (isocitrate dehydrogenase 2) mutant type small-molecule inhibitor and an application thereof in the inhibition and killing of tumor cells. The IDH2 mutant type small-molecule inhibitor can be used for treating IDH2 mutant type acute myelogenous leukemia, glioma and osteosarcoma and has strong pertinence, the normal physiological activities are not influenced, immature leukocyte can be promoted to be mature, the harm caused to the body of a patient is relatively small, the clinical use effect is relatively good, and the remission rate is relatively high.

The invention belongs to the field of molecular therapy and particularly relates to an IDH2 (isocitrate dehydrogenase 2) mutant type small-molecule inhibitor and an application thereof in the inhibition and killing of tumor cells. The IDH2 mutant type small-molecule inhibitor can be used for treating IDH2 mutant type acute myelogenous leukemia, glioma and osteosarcoma and has strong pertinence, the normal physiological activities are not influenced, immature leukocyte can be promoted to be mature, the harm caused to the body of a patient is relatively small, the clinical use effect is relatively good, and the remission rate is relatively high.

The invention relates to an ADGRE2-targeting chimeric antigen receptor and application thereof. The ADGRE2-targeting chimeric antigen receptor comprises an ADGRE2-targeting single-chain antibody, a hinge region, a transmembrane structural domain, a costimulatory structural domain and a signal transduction structural domain which are sequentially connected from an amino terminal to a carboxyl terminal, the amino acid sequences of a light chain variable region and a heavy chain variable region of the ADGRE2-targeting single-chain antibody are respectively shown as SEQ ID NO: 1 and SEQ ID NO: 2. An ADGRE2-targeting chimeric antigen receptor T cell constructed by using the chimeric antigen receptor can specifically kill ADGRE2 positive tumor cells, so that an effective cell treatment choice is provided for treating ADGRE2 positive acute myelogenous leukemia.

The invention relates to a novel FLT3 kinase inhibitor and synthesis and application thereof, the structural formula of the inhibitor is shown in the specification, wherein the R1, R2, R3 and R4 are respectively and independently one of H, C1-C10 alkyl, C1-C10 alkoxy or halogen. Compared with Quizartinib, the inhibitor synthesized by the invention has the advantages that the IC50 value is in the same order of magnitude or even lower than that of Quizartinib, and the inhibitor can be used for preparing medicines for treating acute myelogenous leukemia.